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Combo shows efficacy in platinum-resistant ovarian cancer
The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.
These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).
“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
Study rationale and details
Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.
At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.
Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.
After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m2 on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).
Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
Efficacy and safety
The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.
As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.
Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.
Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.
Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
Comparison with AURELIA
Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.
According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.
An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.
Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”
“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”
Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.
“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.
The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.
The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.
These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).
“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
Study rationale and details
Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.
At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.
Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.
After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m2 on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).
Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
Efficacy and safety
The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.
As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.
Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.
Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.
Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
Comparison with AURELIA
Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.
According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.
An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.
Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”
“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”
Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.
“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.
The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.
The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.
These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).
“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
Study rationale and details
Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.
At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.
Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.
After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m2 on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).
Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
Efficacy and safety
The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.
As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.
Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.
Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.
Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
Comparison with AURELIA
Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.
According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.
An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.
Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”
“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”
Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.
“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.
The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.
FROM SGO 2021
Call to eradicate all types of HPV cancers, not just cervical
The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.
Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.
One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.
In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.
“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.
“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.
Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.
At present, the WHO advocates only for female vaccination and screening.
Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.
Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.
“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.
“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.
“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.
In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.
Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.
Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
Unethical to leave males out?
Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.
Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.
With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.
On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.
“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
Eliminating cervical cancer
Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.
Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.
However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.
Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.
In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
OPSCC elimination
Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.
HPV-related OPSCCs are mostly associated specifically with HPV 16.
There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.
They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.
The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.
“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”
Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”
The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.
In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.
Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.
The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.
A version of this article first appeared on Medscape.com.
The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.
Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.
One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.
In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.
“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.
“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.
Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.
At present, the WHO advocates only for female vaccination and screening.
Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.
Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.
“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.
“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.
“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.
In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.
Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.
Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
Unethical to leave males out?
Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.
Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.
With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.
On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.
“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
Eliminating cervical cancer
Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.
Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.
However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.
Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.
In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
OPSCC elimination
Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.
HPV-related OPSCCs are mostly associated specifically with HPV 16.
There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.
They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.
The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.
“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”
Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”
The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.
In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.
Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.
The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.
A version of this article first appeared on Medscape.com.
The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.
Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.
One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.
In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.
“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.
“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.
Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.
At present, the WHO advocates only for female vaccination and screening.
Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.
Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.
“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.
“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.
“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.
In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.
Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.
Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
Unethical to leave males out?
Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.
Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.
With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.
On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.
“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
Eliminating cervical cancer
Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.
Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.
However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.
Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.
In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
OPSCC elimination
Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.
HPV-related OPSCCs are mostly associated specifically with HPV 16.
There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.
They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.
The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.
“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”
Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”
The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.
In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.
Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.
The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.
A version of this article first appeared on Medscape.com.
Niraparib maintenance offers continued benefit in some with recurrent ovarian cancer
The final analysis showed a significant difference in second progression-free survival (PFS2) with niraparib versus placebo, but only in patients with germline BRCA mutations.
The overall survival analysis was limited because the study was not powered to detect differences in OS. Still, the investigators found a trend toward better OS with niraparib in patients who had germline BRCA mutations.
These results were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11139).
The final analysis of this study was muddied by missing data for many of the 553 patients originally randomized, according to Ursula Matulonis, MD, of the Dana-Farber Cancer Institute in Boston, who presented the study’s results at the meeting.
“Since 2014, approvals of PARP [poly (ADP-ribose) polymerase] inhibitors worldwide in different lines of ovarian cancer therapy have revolutionized the treatment of women with ovarian cancer,” Dr. Matulonis said. “During the time from the initial results of the NOVA study in 2016 to this final analysis, PARP inhibitors have become available commercially globally.”
The wider availability of PARP inhibitors led to premature unblinding and withdrawals from the trial, resulting in missing data for a large proportion of patients.
Initial results
In the primary analysis of the trial, the median PFS was 21 months among patients with germline BRCA mutations who received niraparib and 5.5 months for patients with germline BRCA mutations who received placebo (P < .001).
Among patients with no germline BRCA mutations, the median PFS was 9.3 months for those who received niraparib and 3.9 months for placebo-treated controls (P < .001).
At the time of the primary PFS analysis in 2016, 155 of the 553 patients originally enrolled had left the study for reasons other than death.
In both treatment cohorts, a large number of patients were unblinded as to their treatment assignments by investigators, which required them to withdraw consent from the study under the protocol, resulting in the aforementioned loss of some data on subsequent therapy and survival status.
Final results: PFS2 and OS
At the time of the final data lock on Oct. 1, 2020, the mean follow-up was 67 months (5.6 years).
In all, 64 patients originally assigned to niraparib were still on study (28 in the germline BRCA mutation cohort and 36 in the nonmutated cohort), as were 28 patients originally assigned to placebo (9 and 19, respectively).
For the final analysis, the investigators were able to retrieve survival data on 51% of the patients originally enrolled, either through protocol amendments and obtaining consent again or through national databases.
Although crossover to the niraparib arm was not allowed on study, patients could receive a PARP inhibitor following disease progression or study withdrawal. Because of discontinuations, data on postprogression therapy were missing for 138 of the 553 patients (25%).
The hazard ratio for PFS2 with niraparib versus placebo was 0.67 for patients with germline BRCA mutations (95% confidence interval, 0.479-0.948) and 0.81 for patients without the mutations (95% CI, 0.632-1.050).
In an analysis adjusted for subsequent PARP inhibitor therapy, there was no significant difference in median OS between the niraparib and placebo arms, regardless of mutation status. In the cohort without BRCA mutations, the median OS was 31.3 months with niraparib and 35.9 months with placebo (HR, 0.97; 95% CI, 0.74-1.26).
However, there was a trend toward improved OS with niraparib among patients with germline BRCA mutations. The median OS was 43.8 months with niraparib and 34.1 months with placebo (HR, 0.66; 95% CI, 0.44-0.99).
Safety: MDS/AML
Hematologic treatment-emergent adverse events occurred primarily in the first year of niraparib treatment. The incidence of grade 3 or greater thrombocytopenia decreased from 33.8% at 1 year to 2.8% in years 2-3. The incidence of anemia decreased from 25.6% to 0.7%, and the neutropenia incidence decreased from 19.3% to 2.1%.
At last follow-up, 13 patients in the niraparib arm (3.5%) and 3 in the placebo arm (1.7%) had developed myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).
The incidence of MDS/AML was 6.6% among patients with germline BRCA mutations who received niraparib, noted invited discussant Deborah K. Armstrong, MD, of the Johns Hopkins Kimmel Cancer Center in Baltimore.
That incidence was nearly as high as the 8% incidence of MDS/AML seen among similar patients in the SOLO-2 trial of olaparib maintenance, she noted.
This observation raises the question “of whether more extensive prior therapy or the longer duration of PARP inhibitor therapy in patients who have recurrent platinum-sensitive disease is the biggest contributor to that,” she said.
Dr. Armstrong commented that it remains to be seen whether the incidence of MDS/AML will increase with longer follow-up, particularly among patients who were more heavily pretreated with chemotherapy prior to PARP inhibitor maintenance, and in patients who remain on a PARP inhibitor until progression in ongoing trials of PARP inhibitors as frontline therapy.
The ENGOT-OV16/NOVA trial was funded by GlaxoSmithKline. Dr. Matulonis reported consulting/advisory fees from Merck, Novartis, and NextCure. Dr. Armstrong disclosed relationships with several companies, not including GlaxoSmithKline.
The final analysis showed a significant difference in second progression-free survival (PFS2) with niraparib versus placebo, but only in patients with germline BRCA mutations.
The overall survival analysis was limited because the study was not powered to detect differences in OS. Still, the investigators found a trend toward better OS with niraparib in patients who had germline BRCA mutations.
These results were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11139).
The final analysis of this study was muddied by missing data for many of the 553 patients originally randomized, according to Ursula Matulonis, MD, of the Dana-Farber Cancer Institute in Boston, who presented the study’s results at the meeting.
“Since 2014, approvals of PARP [poly (ADP-ribose) polymerase] inhibitors worldwide in different lines of ovarian cancer therapy have revolutionized the treatment of women with ovarian cancer,” Dr. Matulonis said. “During the time from the initial results of the NOVA study in 2016 to this final analysis, PARP inhibitors have become available commercially globally.”
The wider availability of PARP inhibitors led to premature unblinding and withdrawals from the trial, resulting in missing data for a large proportion of patients.
Initial results
In the primary analysis of the trial, the median PFS was 21 months among patients with germline BRCA mutations who received niraparib and 5.5 months for patients with germline BRCA mutations who received placebo (P < .001).
Among patients with no germline BRCA mutations, the median PFS was 9.3 months for those who received niraparib and 3.9 months for placebo-treated controls (P < .001).
At the time of the primary PFS analysis in 2016, 155 of the 553 patients originally enrolled had left the study for reasons other than death.
In both treatment cohorts, a large number of patients were unblinded as to their treatment assignments by investigators, which required them to withdraw consent from the study under the protocol, resulting in the aforementioned loss of some data on subsequent therapy and survival status.
Final results: PFS2 and OS
At the time of the final data lock on Oct. 1, 2020, the mean follow-up was 67 months (5.6 years).
In all, 64 patients originally assigned to niraparib were still on study (28 in the germline BRCA mutation cohort and 36 in the nonmutated cohort), as were 28 patients originally assigned to placebo (9 and 19, respectively).
For the final analysis, the investigators were able to retrieve survival data on 51% of the patients originally enrolled, either through protocol amendments and obtaining consent again or through national databases.
Although crossover to the niraparib arm was not allowed on study, patients could receive a PARP inhibitor following disease progression or study withdrawal. Because of discontinuations, data on postprogression therapy were missing for 138 of the 553 patients (25%).
The hazard ratio for PFS2 with niraparib versus placebo was 0.67 for patients with germline BRCA mutations (95% confidence interval, 0.479-0.948) and 0.81 for patients without the mutations (95% CI, 0.632-1.050).
In an analysis adjusted for subsequent PARP inhibitor therapy, there was no significant difference in median OS between the niraparib and placebo arms, regardless of mutation status. In the cohort without BRCA mutations, the median OS was 31.3 months with niraparib and 35.9 months with placebo (HR, 0.97; 95% CI, 0.74-1.26).
However, there was a trend toward improved OS with niraparib among patients with germline BRCA mutations. The median OS was 43.8 months with niraparib and 34.1 months with placebo (HR, 0.66; 95% CI, 0.44-0.99).
Safety: MDS/AML
Hematologic treatment-emergent adverse events occurred primarily in the first year of niraparib treatment. The incidence of grade 3 or greater thrombocytopenia decreased from 33.8% at 1 year to 2.8% in years 2-3. The incidence of anemia decreased from 25.6% to 0.7%, and the neutropenia incidence decreased from 19.3% to 2.1%.
At last follow-up, 13 patients in the niraparib arm (3.5%) and 3 in the placebo arm (1.7%) had developed myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).
The incidence of MDS/AML was 6.6% among patients with germline BRCA mutations who received niraparib, noted invited discussant Deborah K. Armstrong, MD, of the Johns Hopkins Kimmel Cancer Center in Baltimore.
That incidence was nearly as high as the 8% incidence of MDS/AML seen among similar patients in the SOLO-2 trial of olaparib maintenance, she noted.
This observation raises the question “of whether more extensive prior therapy or the longer duration of PARP inhibitor therapy in patients who have recurrent platinum-sensitive disease is the biggest contributor to that,” she said.
Dr. Armstrong commented that it remains to be seen whether the incidence of MDS/AML will increase with longer follow-up, particularly among patients who were more heavily pretreated with chemotherapy prior to PARP inhibitor maintenance, and in patients who remain on a PARP inhibitor until progression in ongoing trials of PARP inhibitors as frontline therapy.
The ENGOT-OV16/NOVA trial was funded by GlaxoSmithKline. Dr. Matulonis reported consulting/advisory fees from Merck, Novartis, and NextCure. Dr. Armstrong disclosed relationships with several companies, not including GlaxoSmithKline.
The final analysis showed a significant difference in second progression-free survival (PFS2) with niraparib versus placebo, but only in patients with germline BRCA mutations.
The overall survival analysis was limited because the study was not powered to detect differences in OS. Still, the investigators found a trend toward better OS with niraparib in patients who had germline BRCA mutations.
These results were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11139).
The final analysis of this study was muddied by missing data for many of the 553 patients originally randomized, according to Ursula Matulonis, MD, of the Dana-Farber Cancer Institute in Boston, who presented the study’s results at the meeting.
“Since 2014, approvals of PARP [poly (ADP-ribose) polymerase] inhibitors worldwide in different lines of ovarian cancer therapy have revolutionized the treatment of women with ovarian cancer,” Dr. Matulonis said. “During the time from the initial results of the NOVA study in 2016 to this final analysis, PARP inhibitors have become available commercially globally.”
The wider availability of PARP inhibitors led to premature unblinding and withdrawals from the trial, resulting in missing data for a large proportion of patients.
Initial results
In the primary analysis of the trial, the median PFS was 21 months among patients with germline BRCA mutations who received niraparib and 5.5 months for patients with germline BRCA mutations who received placebo (P < .001).
Among patients with no germline BRCA mutations, the median PFS was 9.3 months for those who received niraparib and 3.9 months for placebo-treated controls (P < .001).
At the time of the primary PFS analysis in 2016, 155 of the 553 patients originally enrolled had left the study for reasons other than death.
In both treatment cohorts, a large number of patients were unblinded as to their treatment assignments by investigators, which required them to withdraw consent from the study under the protocol, resulting in the aforementioned loss of some data on subsequent therapy and survival status.
Final results: PFS2 and OS
At the time of the final data lock on Oct. 1, 2020, the mean follow-up was 67 months (5.6 years).
In all, 64 patients originally assigned to niraparib were still on study (28 in the germline BRCA mutation cohort and 36 in the nonmutated cohort), as were 28 patients originally assigned to placebo (9 and 19, respectively).
For the final analysis, the investigators were able to retrieve survival data on 51% of the patients originally enrolled, either through protocol amendments and obtaining consent again or through national databases.
Although crossover to the niraparib arm was not allowed on study, patients could receive a PARP inhibitor following disease progression or study withdrawal. Because of discontinuations, data on postprogression therapy were missing for 138 of the 553 patients (25%).
The hazard ratio for PFS2 with niraparib versus placebo was 0.67 for patients with germline BRCA mutations (95% confidence interval, 0.479-0.948) and 0.81 for patients without the mutations (95% CI, 0.632-1.050).
In an analysis adjusted for subsequent PARP inhibitor therapy, there was no significant difference in median OS between the niraparib and placebo arms, regardless of mutation status. In the cohort without BRCA mutations, the median OS was 31.3 months with niraparib and 35.9 months with placebo (HR, 0.97; 95% CI, 0.74-1.26).
However, there was a trend toward improved OS with niraparib among patients with germline BRCA mutations. The median OS was 43.8 months with niraparib and 34.1 months with placebo (HR, 0.66; 95% CI, 0.44-0.99).
Safety: MDS/AML
Hematologic treatment-emergent adverse events occurred primarily in the first year of niraparib treatment. The incidence of grade 3 or greater thrombocytopenia decreased from 33.8% at 1 year to 2.8% in years 2-3. The incidence of anemia decreased from 25.6% to 0.7%, and the neutropenia incidence decreased from 19.3% to 2.1%.
At last follow-up, 13 patients in the niraparib arm (3.5%) and 3 in the placebo arm (1.7%) had developed myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).
The incidence of MDS/AML was 6.6% among patients with germline BRCA mutations who received niraparib, noted invited discussant Deborah K. Armstrong, MD, of the Johns Hopkins Kimmel Cancer Center in Baltimore.
That incidence was nearly as high as the 8% incidence of MDS/AML seen among similar patients in the SOLO-2 trial of olaparib maintenance, she noted.
This observation raises the question “of whether more extensive prior therapy or the longer duration of PARP inhibitor therapy in patients who have recurrent platinum-sensitive disease is the biggest contributor to that,” she said.
Dr. Armstrong commented that it remains to be seen whether the incidence of MDS/AML will increase with longer follow-up, particularly among patients who were more heavily pretreated with chemotherapy prior to PARP inhibitor maintenance, and in patients who remain on a PARP inhibitor until progression in ongoing trials of PARP inhibitors as frontline therapy.
The ENGOT-OV16/NOVA trial was funded by GlaxoSmithKline. Dr. Matulonis reported consulting/advisory fees from Merck, Novartis, and NextCure. Dr. Armstrong disclosed relationships with several companies, not including GlaxoSmithKline.
FROM SGO 2021
Biomarkers predict efficacy of DKN-01 in endometrial cancer
Among 29 patients with heavily pretreated EEC, outcomes of DKN-01 monotherapy were best in patients with Wnt activating mutations, high levels of DKK1 expression, or PIK3CA activating mutations.
Patients in these groups had better disease control rates and progression-free survival (PFS), reported Rebecca C. Arend, MD, of the University of Alabama at Birmingham.
“Future development will focus on biomarker-selected patients, specifically patients with Wnt activating mutations, high tumoral DKK1, and PIK3CA activating mutations,” Dr. Arend said at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10717).
She explained that DKK1 has been shown to modulate signaling in the Wnt/beta-catenin pathway, a key regulator of cellular functions in humans and animals that has been highly conserved throughout evolution.
“DKK1 activates P13 kinase/AKT signaling by binding to the CKAP4 receptor to promote tumor growth,” Dr. Arend explained.
Focus on monotherapy
Dr. Arend and colleagues conducted a phase 2 basket trial of DKN-01 either as monotherapy or in combination with paclitaxel in patients with EEC, epithelial ovarian cancer, and carcinosarcoma (malignant mixed Mullerian tumor). The trial design required at least 50% of patients to have Wnt signaling alterations.
Dr. Arend reported results for 29 patients with EEC who received DKN-01 monotherapy.
There were nine patients with Wnt activating mutations. None of them achieved a complete response (CR) or partial response (PR), but six had stable disease (SD), for a disease control rate of 67%. Of the 20 patients without Wnt activating mutations, 1 achieved a CR, 1 achieved a PR, and 3 had SD, for a disease control rate of 25%.
The median PFS was 5.5 months in patients with Wnt activating mutations and 1.8 months in patients without the mutations.
“Importantly, patients whose tumors have a Wnt activating mutation have a correlation with increased tumoral expression of DKK1 by 14.4-fold higher,” Dr. Arend noted.
When she and her colleagues analyzed patients by DKK1 expression, the team found that high levels of DKK1 correlated with better clinical outcomes. The disease control rate was 57% for patients in the highest third of DKK1 expression (1 PR, 3 SD) vs. 7% (1 SD) for those in the lowest two-thirds. The median PFS was 3 months and 1.8 months, respectively.
Of the seven patients whose tumors could not be evaluated for DKK1 expression, one patient had a CR and 5 had SD, for a disease control rate of 86%. The median PFS in this group was 8.0 months. Three of these patients had known Wnt activating mutations.
“Given this correlation [between] higher DKK1 expression [and] Wnt activating mutations, one could consider that, at a minimum, these patients would have had a higher DKK1 expression as well,” Dr. Arend said.
She and her colleagues also found that patients with PIK3CA activating mutations and two or fewer prior lines of therapy had a 33% overall response rate (1 CR, 1 PR), compared with 0% for patients without these mutations who had two or fewer prior therapies. Patients with PIK3CA activating mutations also had a better disease control rate (67% vs. 40%) and median PFS (5.6 months vs. 1.8 months).
Although Dr. Arend did not present safety data from the study at SGO 2021, she reported some data in a video investor call for Leap Therapeutics, which is developing DKN-01. She said the most common treatment-emergent adverse events with DKN-01 were nausea in 28.8% of patients, fatigue in 26.7%, and constipation in 11.5%. Serious events included acute kidney injury, dyspnea, nausea, and peripheral edema (occurring in 1.9% of patients each).
Monotherapy or combination?
In the question-and-answer session following Dr. Arend’s presentation, comoderator Joyce Liu, MD, of the Dana-Farber Cancer Institute in Boston, said that “even in the DKK1-high tumors, the activity of DKN-01 as a monotherapy is a little bit limited.”
She asked whether the future of targeting inhibitors in the Wnt/beta-catenin pathway will be limited to biomarker-specific populations or if agents such as DKN-01 should be used in combinations.
“I do think that we need a lot more data to determine,” Dr. Arend replied. “I think that there may be a subset of patients, especially those that don’t tolerate the [lenvatinib/pembrolizumab] combo who may have an upregulation of beta-catenin or a Wnt mutation who could benefit from monotherapy.”
Dr. Arend added that data from her lab and others suggest that DKN-01 in combination with other agents holds promise for improving outcomes in biomarker-selected populations.
The current study is funded by Leap Therapeutics. Dr. Arend disclosed advisory board activity for the company and others. Dr. Liu reported personal fees from several companies, not including Leap Therapeutics.
Among 29 patients with heavily pretreated EEC, outcomes of DKN-01 monotherapy were best in patients with Wnt activating mutations, high levels of DKK1 expression, or PIK3CA activating mutations.
Patients in these groups had better disease control rates and progression-free survival (PFS), reported Rebecca C. Arend, MD, of the University of Alabama at Birmingham.
“Future development will focus on biomarker-selected patients, specifically patients with Wnt activating mutations, high tumoral DKK1, and PIK3CA activating mutations,” Dr. Arend said at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10717).
She explained that DKK1 has been shown to modulate signaling in the Wnt/beta-catenin pathway, a key regulator of cellular functions in humans and animals that has been highly conserved throughout evolution.
“DKK1 activates P13 kinase/AKT signaling by binding to the CKAP4 receptor to promote tumor growth,” Dr. Arend explained.
Focus on monotherapy
Dr. Arend and colleagues conducted a phase 2 basket trial of DKN-01 either as monotherapy or in combination with paclitaxel in patients with EEC, epithelial ovarian cancer, and carcinosarcoma (malignant mixed Mullerian tumor). The trial design required at least 50% of patients to have Wnt signaling alterations.
Dr. Arend reported results for 29 patients with EEC who received DKN-01 monotherapy.
There were nine patients with Wnt activating mutations. None of them achieved a complete response (CR) or partial response (PR), but six had stable disease (SD), for a disease control rate of 67%. Of the 20 patients without Wnt activating mutations, 1 achieved a CR, 1 achieved a PR, and 3 had SD, for a disease control rate of 25%.
The median PFS was 5.5 months in patients with Wnt activating mutations and 1.8 months in patients without the mutations.
“Importantly, patients whose tumors have a Wnt activating mutation have a correlation with increased tumoral expression of DKK1 by 14.4-fold higher,” Dr. Arend noted.
When she and her colleagues analyzed patients by DKK1 expression, the team found that high levels of DKK1 correlated with better clinical outcomes. The disease control rate was 57% for patients in the highest third of DKK1 expression (1 PR, 3 SD) vs. 7% (1 SD) for those in the lowest two-thirds. The median PFS was 3 months and 1.8 months, respectively.
Of the seven patients whose tumors could not be evaluated for DKK1 expression, one patient had a CR and 5 had SD, for a disease control rate of 86%. The median PFS in this group was 8.0 months. Three of these patients had known Wnt activating mutations.
“Given this correlation [between] higher DKK1 expression [and] Wnt activating mutations, one could consider that, at a minimum, these patients would have had a higher DKK1 expression as well,” Dr. Arend said.
She and her colleagues also found that patients with PIK3CA activating mutations and two or fewer prior lines of therapy had a 33% overall response rate (1 CR, 1 PR), compared with 0% for patients without these mutations who had two or fewer prior therapies. Patients with PIK3CA activating mutations also had a better disease control rate (67% vs. 40%) and median PFS (5.6 months vs. 1.8 months).
Although Dr. Arend did not present safety data from the study at SGO 2021, she reported some data in a video investor call for Leap Therapeutics, which is developing DKN-01. She said the most common treatment-emergent adverse events with DKN-01 were nausea in 28.8% of patients, fatigue in 26.7%, and constipation in 11.5%. Serious events included acute kidney injury, dyspnea, nausea, and peripheral edema (occurring in 1.9% of patients each).
Monotherapy or combination?
In the question-and-answer session following Dr. Arend’s presentation, comoderator Joyce Liu, MD, of the Dana-Farber Cancer Institute in Boston, said that “even in the DKK1-high tumors, the activity of DKN-01 as a monotherapy is a little bit limited.”
She asked whether the future of targeting inhibitors in the Wnt/beta-catenin pathway will be limited to biomarker-specific populations or if agents such as DKN-01 should be used in combinations.
“I do think that we need a lot more data to determine,” Dr. Arend replied. “I think that there may be a subset of patients, especially those that don’t tolerate the [lenvatinib/pembrolizumab] combo who may have an upregulation of beta-catenin or a Wnt mutation who could benefit from monotherapy.”
Dr. Arend added that data from her lab and others suggest that DKN-01 in combination with other agents holds promise for improving outcomes in biomarker-selected populations.
The current study is funded by Leap Therapeutics. Dr. Arend disclosed advisory board activity for the company and others. Dr. Liu reported personal fees from several companies, not including Leap Therapeutics.
Among 29 patients with heavily pretreated EEC, outcomes of DKN-01 monotherapy were best in patients with Wnt activating mutations, high levels of DKK1 expression, or PIK3CA activating mutations.
Patients in these groups had better disease control rates and progression-free survival (PFS), reported Rebecca C. Arend, MD, of the University of Alabama at Birmingham.
“Future development will focus on biomarker-selected patients, specifically patients with Wnt activating mutations, high tumoral DKK1, and PIK3CA activating mutations,” Dr. Arend said at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10717).
She explained that DKK1 has been shown to modulate signaling in the Wnt/beta-catenin pathway, a key regulator of cellular functions in humans and animals that has been highly conserved throughout evolution.
“DKK1 activates P13 kinase/AKT signaling by binding to the CKAP4 receptor to promote tumor growth,” Dr. Arend explained.
Focus on monotherapy
Dr. Arend and colleagues conducted a phase 2 basket trial of DKN-01 either as monotherapy or in combination with paclitaxel in patients with EEC, epithelial ovarian cancer, and carcinosarcoma (malignant mixed Mullerian tumor). The trial design required at least 50% of patients to have Wnt signaling alterations.
Dr. Arend reported results for 29 patients with EEC who received DKN-01 monotherapy.
There were nine patients with Wnt activating mutations. None of them achieved a complete response (CR) or partial response (PR), but six had stable disease (SD), for a disease control rate of 67%. Of the 20 patients without Wnt activating mutations, 1 achieved a CR, 1 achieved a PR, and 3 had SD, for a disease control rate of 25%.
The median PFS was 5.5 months in patients with Wnt activating mutations and 1.8 months in patients without the mutations.
“Importantly, patients whose tumors have a Wnt activating mutation have a correlation with increased tumoral expression of DKK1 by 14.4-fold higher,” Dr. Arend noted.
When she and her colleagues analyzed patients by DKK1 expression, the team found that high levels of DKK1 correlated with better clinical outcomes. The disease control rate was 57% for patients in the highest third of DKK1 expression (1 PR, 3 SD) vs. 7% (1 SD) for those in the lowest two-thirds. The median PFS was 3 months and 1.8 months, respectively.
Of the seven patients whose tumors could not be evaluated for DKK1 expression, one patient had a CR and 5 had SD, for a disease control rate of 86%. The median PFS in this group was 8.0 months. Three of these patients had known Wnt activating mutations.
“Given this correlation [between] higher DKK1 expression [and] Wnt activating mutations, one could consider that, at a minimum, these patients would have had a higher DKK1 expression as well,” Dr. Arend said.
She and her colleagues also found that patients with PIK3CA activating mutations and two or fewer prior lines of therapy had a 33% overall response rate (1 CR, 1 PR), compared with 0% for patients without these mutations who had two or fewer prior therapies. Patients with PIK3CA activating mutations also had a better disease control rate (67% vs. 40%) and median PFS (5.6 months vs. 1.8 months).
Although Dr. Arend did not present safety data from the study at SGO 2021, she reported some data in a video investor call for Leap Therapeutics, which is developing DKN-01. She said the most common treatment-emergent adverse events with DKN-01 were nausea in 28.8% of patients, fatigue in 26.7%, and constipation in 11.5%. Serious events included acute kidney injury, dyspnea, nausea, and peripheral edema (occurring in 1.9% of patients each).
Monotherapy or combination?
In the question-and-answer session following Dr. Arend’s presentation, comoderator Joyce Liu, MD, of the Dana-Farber Cancer Institute in Boston, said that “even in the DKK1-high tumors, the activity of DKN-01 as a monotherapy is a little bit limited.”
She asked whether the future of targeting inhibitors in the Wnt/beta-catenin pathway will be limited to biomarker-specific populations or if agents such as DKN-01 should be used in combinations.
“I do think that we need a lot more data to determine,” Dr. Arend replied. “I think that there may be a subset of patients, especially those that don’t tolerate the [lenvatinib/pembrolizumab] combo who may have an upregulation of beta-catenin or a Wnt mutation who could benefit from monotherapy.”
Dr. Arend added that data from her lab and others suggest that DKN-01 in combination with other agents holds promise for improving outcomes in biomarker-selected populations.
The current study is funded by Leap Therapeutics. Dr. Arend disclosed advisory board activity for the company and others. Dr. Liu reported personal fees from several companies, not including Leap Therapeutics.
FROM SGO 2021
The significance of mismatch repair deficiency in endometrial cancer
Women with Lynch syndrome are known to carry an approximately 60% lifetime risk of endometrial cancer. These cancers result from inherited deleterious mutations in genes that code for mismatch repair proteins. However, mismatch repair deficiency (MMR-d) is not exclusively found in the tumors of patients with Lynch syndrome, and much is being learned about this group of endometrial cancers, their behavior, and their vulnerability to targeted therapies.
During the processes of DNA replication, recombination, or chemical and physical damage, mismatches in base pairs frequently occurs. Mismatch repair proteins function to identify and repair such errors, and the loss of their function causes the accumulation of the insertions or deletions of short, repetitive sequences of DNA. This phenomenon can be measured using polymerase chain reaction (PCR) screening of known microsatellites to look for the accumulation of errors, a phenotype which is called microsatellite instability (MSI). The accumulation of errors in DNA sequences is thought to lead to mutations in cancer-related genes.
The four predominant mismatch repair genes include MLH1, MSH2, MSH 6, and PMS2. These genes may possess loss of function through a germline/inherited mechanism, such as Lynch syndrome, or can be sporadically acquired. Approximately 20%-30% of endometrial cancers exhibit MMR-d with acquired, sporadic losses in function being the majority of cases and only approximately 10% a result of Lynch syndrome. Mutations in PMS2 are the dominant genotype of Lynch syndrome, whereas loss of function in MLH1 is most frequent aberration in sporadic cases of MMR-d endometrial cancer.1
Endometrial cancers can be tested for MMR-d by performing immunohistochemistry to look for loss of expression in the four most common MMR genes. If there is loss of expression of MLH1, additional triage testing can be performed to determine if this loss is caused by the epigenetic phenomenon of hypermethylation. When present, this excludes Lynch syndrome and suggests a sporadic form origin of the disease. If there is loss of expression of the MMR genes (including loss of MLH1 and subsequent negative testing for promotor methylation), the patient should receive genetic testing for the presence of a germline mutation indicating Lynch syndrome. As an adjunct or alternative to immunohistochemistry, PCR studies or next-generation sequencing can be used to measure the presence of microsatellite instability in a process that identifies the expansion or reduction in repetitive DNA sequences of the tumor, compared with normal tumor.2
It is of the highest importance to identify endometrial cancers caused by Lynch syndrome because this enables providers to offer cascade testing of relatives, and to intensify screening or preventative measures for the many other cancers (such as colon, upper gastrointestinal, breast, and urothelial) for which these patients are at risk. Therefore, routine screening for MMR-d tumors is recommended in all cases of endometrial cancer, not simply those of a young age at diagnosis or for whom a strong family history exists.3 Using family history factors, primary tumor site, and age as a trigger for screening for Lynch syndrome, such as the Bethesda Guidelines, is associated with a 82% sensitivity in identifying Lynch syndrome. In a meta-analysis including testing results from 1,159 women with endometrial cancer, 43% of patients who were diagnosed with Lynch syndrome via molecular analysis would have been missed by clinical screening using Bethesda Guidelines.2
Discovering cases of Lynch syndrome is not the only benefit of routine testing for MMR-d in endometrial cancers. There is also significant value in the characterization of sporadic mismatch repair–deficient tumors because this information provides prognostic information and guides therapy. Tumors with a microsatellite-high phenotype/MMR-d were identified as one of the four distinct molecular subgroups of endometrial cancer by the Cancer Genome Atlas.4 Patients with this molecular profile exhibited “intermediate” prognostic outcomes, performing better than the “serous-like” cancers with p53 mutations, yet worse than patients with a POLE ultramutated group who rarely experience recurrences or death, even in the setting of unfavorable histology.
Beyond prognostication, the molecular profile of endometrial cancers also influence their responsiveness to therapeutics, highlighting the importance of splitting, not lumping endometrial cancers into relevant molecular subgroups when designing research and practicing clinical medicine. The PORTEC-3 trial studied 410 women with high-risk endometrial cancer, and randomized participants to receive either adjuvant radiation alone, or radiation with chemotherapy.5 There were no differences in progression-free survival between the two therapeutic strategies when analyzed in aggregate. However, when analyzed by Cancer Genome Atlas molecular subgroup, it was noted that there was a clear benefit from chemotherapy for patients with p53 mutations. For patients with MMR-d tumors, no such benefit was observed. Patients assigned this molecular subgroup did no better with the addition of platinum and taxane chemotherapy over radiation alone. Unfortunately, for patients with MMR-d tumors, recurrence rates remained high, suggesting that we can and need to discover more effective therapies for these tumors than what is available with conventional radiation or platinum and taxane chemotherapy. Targeted therapy may be the solution to this problem. Through microsatellite instability, MMR-d tumors create somatic mutations which result in neoantigens, an immunogenic environment. This state up-regulates checkpoint inhibitor proteins, which serve as an actionable target for anti-PD-L1 antibodies, such as the drug pembrolizumab which has been shown to be highly active against MMR-d endometrial cancer. In the landmark, KEYNOTE-158 trial, patients with advanced, recurrent solid tumors that exhibited MMR-d were treated with pembrolizumab.6 This included 49 patients with endometrial cancer, among whom there was a 79% response rate. Subsequently, pembrolizumab was granted Food and Drug Administration approval for use in advanced, recurrent MMR-d/MSI-high endometrial cancer. Trials are currently enrolling patients to explore the utility of this drug in the up-front setting in both early- and late-stage disease with a hope that this targeted therapy can do what conventional cytotoxic chemotherapy has failed to do.
Therefore, given the clinical significance of mismatch repair deficiency, all patients with endometrial cancer should be investigated for loss of expression in these proteins, and if present, considered for the possibility of Lynch syndrome. While most will not have an inherited cause, this information regarding their tumor biology remains critically important in both prognostication and decision-making surrounding other therapies and their eligibility for promising clinical trials.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to declare. Email her at [email protected].
References
1. Simpkins SB et al. Hum. Mol. Genet. 1999;8:661-6.
2. Kahn R et al. Cancer. 2019 Sep 15;125(18):2172-3183.
3. SGO Clinical Practice Statement: Screening for Lynch Syndrome in Endometrial Cancer. https://www.sgo.org/clinical-practice/guidelines/screening-for-lynch-syndrome-in-endometrial-cancer/
4. Kandoth et al. Nature. 2013;497(7447):67-73.
5. Leon-Castillo A et al. J Clin Oncol. 2020 Oct 10;38(29):3388-97.
6. Marabelle A et al. J Clin Oncol. 2020 Jan 1;38(1):1-10.
Women with Lynch syndrome are known to carry an approximately 60% lifetime risk of endometrial cancer. These cancers result from inherited deleterious mutations in genes that code for mismatch repair proteins. However, mismatch repair deficiency (MMR-d) is not exclusively found in the tumors of patients with Lynch syndrome, and much is being learned about this group of endometrial cancers, their behavior, and their vulnerability to targeted therapies.
During the processes of DNA replication, recombination, or chemical and physical damage, mismatches in base pairs frequently occurs. Mismatch repair proteins function to identify and repair such errors, and the loss of their function causes the accumulation of the insertions or deletions of short, repetitive sequences of DNA. This phenomenon can be measured using polymerase chain reaction (PCR) screening of known microsatellites to look for the accumulation of errors, a phenotype which is called microsatellite instability (MSI). The accumulation of errors in DNA sequences is thought to lead to mutations in cancer-related genes.
The four predominant mismatch repair genes include MLH1, MSH2, MSH 6, and PMS2. These genes may possess loss of function through a germline/inherited mechanism, such as Lynch syndrome, or can be sporadically acquired. Approximately 20%-30% of endometrial cancers exhibit MMR-d with acquired, sporadic losses in function being the majority of cases and only approximately 10% a result of Lynch syndrome. Mutations in PMS2 are the dominant genotype of Lynch syndrome, whereas loss of function in MLH1 is most frequent aberration in sporadic cases of MMR-d endometrial cancer.1
Endometrial cancers can be tested for MMR-d by performing immunohistochemistry to look for loss of expression in the four most common MMR genes. If there is loss of expression of MLH1, additional triage testing can be performed to determine if this loss is caused by the epigenetic phenomenon of hypermethylation. When present, this excludes Lynch syndrome and suggests a sporadic form origin of the disease. If there is loss of expression of the MMR genes (including loss of MLH1 and subsequent negative testing for promotor methylation), the patient should receive genetic testing for the presence of a germline mutation indicating Lynch syndrome. As an adjunct or alternative to immunohistochemistry, PCR studies or next-generation sequencing can be used to measure the presence of microsatellite instability in a process that identifies the expansion or reduction in repetitive DNA sequences of the tumor, compared with normal tumor.2
It is of the highest importance to identify endometrial cancers caused by Lynch syndrome because this enables providers to offer cascade testing of relatives, and to intensify screening or preventative measures for the many other cancers (such as colon, upper gastrointestinal, breast, and urothelial) for which these patients are at risk. Therefore, routine screening for MMR-d tumors is recommended in all cases of endometrial cancer, not simply those of a young age at diagnosis or for whom a strong family history exists.3 Using family history factors, primary tumor site, and age as a trigger for screening for Lynch syndrome, such as the Bethesda Guidelines, is associated with a 82% sensitivity in identifying Lynch syndrome. In a meta-analysis including testing results from 1,159 women with endometrial cancer, 43% of patients who were diagnosed with Lynch syndrome via molecular analysis would have been missed by clinical screening using Bethesda Guidelines.2
Discovering cases of Lynch syndrome is not the only benefit of routine testing for MMR-d in endometrial cancers. There is also significant value in the characterization of sporadic mismatch repair–deficient tumors because this information provides prognostic information and guides therapy. Tumors with a microsatellite-high phenotype/MMR-d were identified as one of the four distinct molecular subgroups of endometrial cancer by the Cancer Genome Atlas.4 Patients with this molecular profile exhibited “intermediate” prognostic outcomes, performing better than the “serous-like” cancers with p53 mutations, yet worse than patients with a POLE ultramutated group who rarely experience recurrences or death, even in the setting of unfavorable histology.
Beyond prognostication, the molecular profile of endometrial cancers also influence their responsiveness to therapeutics, highlighting the importance of splitting, not lumping endometrial cancers into relevant molecular subgroups when designing research and practicing clinical medicine. The PORTEC-3 trial studied 410 women with high-risk endometrial cancer, and randomized participants to receive either adjuvant radiation alone, or radiation with chemotherapy.5 There were no differences in progression-free survival between the two therapeutic strategies when analyzed in aggregate. However, when analyzed by Cancer Genome Atlas molecular subgroup, it was noted that there was a clear benefit from chemotherapy for patients with p53 mutations. For patients with MMR-d tumors, no such benefit was observed. Patients assigned this molecular subgroup did no better with the addition of platinum and taxane chemotherapy over radiation alone. Unfortunately, for patients with MMR-d tumors, recurrence rates remained high, suggesting that we can and need to discover more effective therapies for these tumors than what is available with conventional radiation or platinum and taxane chemotherapy. Targeted therapy may be the solution to this problem. Through microsatellite instability, MMR-d tumors create somatic mutations which result in neoantigens, an immunogenic environment. This state up-regulates checkpoint inhibitor proteins, which serve as an actionable target for anti-PD-L1 antibodies, such as the drug pembrolizumab which has been shown to be highly active against MMR-d endometrial cancer. In the landmark, KEYNOTE-158 trial, patients with advanced, recurrent solid tumors that exhibited MMR-d were treated with pembrolizumab.6 This included 49 patients with endometrial cancer, among whom there was a 79% response rate. Subsequently, pembrolizumab was granted Food and Drug Administration approval for use in advanced, recurrent MMR-d/MSI-high endometrial cancer. Trials are currently enrolling patients to explore the utility of this drug in the up-front setting in both early- and late-stage disease with a hope that this targeted therapy can do what conventional cytotoxic chemotherapy has failed to do.
Therefore, given the clinical significance of mismatch repair deficiency, all patients with endometrial cancer should be investigated for loss of expression in these proteins, and if present, considered for the possibility of Lynch syndrome. While most will not have an inherited cause, this information regarding their tumor biology remains critically important in both prognostication and decision-making surrounding other therapies and their eligibility for promising clinical trials.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to declare. Email her at [email protected].
References
1. Simpkins SB et al. Hum. Mol. Genet. 1999;8:661-6.
2. Kahn R et al. Cancer. 2019 Sep 15;125(18):2172-3183.
3. SGO Clinical Practice Statement: Screening for Lynch Syndrome in Endometrial Cancer. https://www.sgo.org/clinical-practice/guidelines/screening-for-lynch-syndrome-in-endometrial-cancer/
4. Kandoth et al. Nature. 2013;497(7447):67-73.
5. Leon-Castillo A et al. J Clin Oncol. 2020 Oct 10;38(29):3388-97.
6. Marabelle A et al. J Clin Oncol. 2020 Jan 1;38(1):1-10.
Women with Lynch syndrome are known to carry an approximately 60% lifetime risk of endometrial cancer. These cancers result from inherited deleterious mutations in genes that code for mismatch repair proteins. However, mismatch repair deficiency (MMR-d) is not exclusively found in the tumors of patients with Lynch syndrome, and much is being learned about this group of endometrial cancers, their behavior, and their vulnerability to targeted therapies.
During the processes of DNA replication, recombination, or chemical and physical damage, mismatches in base pairs frequently occurs. Mismatch repair proteins function to identify and repair such errors, and the loss of their function causes the accumulation of the insertions or deletions of short, repetitive sequences of DNA. This phenomenon can be measured using polymerase chain reaction (PCR) screening of known microsatellites to look for the accumulation of errors, a phenotype which is called microsatellite instability (MSI). The accumulation of errors in DNA sequences is thought to lead to mutations in cancer-related genes.
The four predominant mismatch repair genes include MLH1, MSH2, MSH 6, and PMS2. These genes may possess loss of function through a germline/inherited mechanism, such as Lynch syndrome, or can be sporadically acquired. Approximately 20%-30% of endometrial cancers exhibit MMR-d with acquired, sporadic losses in function being the majority of cases and only approximately 10% a result of Lynch syndrome. Mutations in PMS2 are the dominant genotype of Lynch syndrome, whereas loss of function in MLH1 is most frequent aberration in sporadic cases of MMR-d endometrial cancer.1
Endometrial cancers can be tested for MMR-d by performing immunohistochemistry to look for loss of expression in the four most common MMR genes. If there is loss of expression of MLH1, additional triage testing can be performed to determine if this loss is caused by the epigenetic phenomenon of hypermethylation. When present, this excludes Lynch syndrome and suggests a sporadic form origin of the disease. If there is loss of expression of the MMR genes (including loss of MLH1 and subsequent negative testing for promotor methylation), the patient should receive genetic testing for the presence of a germline mutation indicating Lynch syndrome. As an adjunct or alternative to immunohistochemistry, PCR studies or next-generation sequencing can be used to measure the presence of microsatellite instability in a process that identifies the expansion or reduction in repetitive DNA sequences of the tumor, compared with normal tumor.2
It is of the highest importance to identify endometrial cancers caused by Lynch syndrome because this enables providers to offer cascade testing of relatives, and to intensify screening or preventative measures for the many other cancers (such as colon, upper gastrointestinal, breast, and urothelial) for which these patients are at risk. Therefore, routine screening for MMR-d tumors is recommended in all cases of endometrial cancer, not simply those of a young age at diagnosis or for whom a strong family history exists.3 Using family history factors, primary tumor site, and age as a trigger for screening for Lynch syndrome, such as the Bethesda Guidelines, is associated with a 82% sensitivity in identifying Lynch syndrome. In a meta-analysis including testing results from 1,159 women with endometrial cancer, 43% of patients who were diagnosed with Lynch syndrome via molecular analysis would have been missed by clinical screening using Bethesda Guidelines.2
Discovering cases of Lynch syndrome is not the only benefit of routine testing for MMR-d in endometrial cancers. There is also significant value in the characterization of sporadic mismatch repair–deficient tumors because this information provides prognostic information and guides therapy. Tumors with a microsatellite-high phenotype/MMR-d were identified as one of the four distinct molecular subgroups of endometrial cancer by the Cancer Genome Atlas.4 Patients with this molecular profile exhibited “intermediate” prognostic outcomes, performing better than the “serous-like” cancers with p53 mutations, yet worse than patients with a POLE ultramutated group who rarely experience recurrences or death, even in the setting of unfavorable histology.
Beyond prognostication, the molecular profile of endometrial cancers also influence their responsiveness to therapeutics, highlighting the importance of splitting, not lumping endometrial cancers into relevant molecular subgroups when designing research and practicing clinical medicine. The PORTEC-3 trial studied 410 women with high-risk endometrial cancer, and randomized participants to receive either adjuvant radiation alone, or radiation with chemotherapy.5 There were no differences in progression-free survival between the two therapeutic strategies when analyzed in aggregate. However, when analyzed by Cancer Genome Atlas molecular subgroup, it was noted that there was a clear benefit from chemotherapy for patients with p53 mutations. For patients with MMR-d tumors, no such benefit was observed. Patients assigned this molecular subgroup did no better with the addition of platinum and taxane chemotherapy over radiation alone. Unfortunately, for patients with MMR-d tumors, recurrence rates remained high, suggesting that we can and need to discover more effective therapies for these tumors than what is available with conventional radiation or platinum and taxane chemotherapy. Targeted therapy may be the solution to this problem. Through microsatellite instability, MMR-d tumors create somatic mutations which result in neoantigens, an immunogenic environment. This state up-regulates checkpoint inhibitor proteins, which serve as an actionable target for anti-PD-L1 antibodies, such as the drug pembrolizumab which has been shown to be highly active against MMR-d endometrial cancer. In the landmark, KEYNOTE-158 trial, patients with advanced, recurrent solid tumors that exhibited MMR-d were treated with pembrolizumab.6 This included 49 patients with endometrial cancer, among whom there was a 79% response rate. Subsequently, pembrolizumab was granted Food and Drug Administration approval for use in advanced, recurrent MMR-d/MSI-high endometrial cancer. Trials are currently enrolling patients to explore the utility of this drug in the up-front setting in both early- and late-stage disease with a hope that this targeted therapy can do what conventional cytotoxic chemotherapy has failed to do.
Therefore, given the clinical significance of mismatch repair deficiency, all patients with endometrial cancer should be investigated for loss of expression in these proteins, and if present, considered for the possibility of Lynch syndrome. While most will not have an inherited cause, this information regarding their tumor biology remains critically important in both prognostication and decision-making surrounding other therapies and their eligibility for promising clinical trials.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to declare. Email her at [email protected].
References
1. Simpkins SB et al. Hum. Mol. Genet. 1999;8:661-6.
2. Kahn R et al. Cancer. 2019 Sep 15;125(18):2172-3183.
3. SGO Clinical Practice Statement: Screening for Lynch Syndrome in Endometrial Cancer. https://www.sgo.org/clinical-practice/guidelines/screening-for-lynch-syndrome-in-endometrial-cancer/
4. Kandoth et al. Nature. 2013;497(7447):67-73.
5. Leon-Castillo A et al. J Clin Oncol. 2020 Oct 10;38(29):3388-97.
6. Marabelle A et al. J Clin Oncol. 2020 Jan 1;38(1):1-10.
Gynecologic cancer patients at risk of insurance loss, ‘catastrophic’ costs
A retrospective study of respondents to the Medical Expenditure Panel Survey showed that more than one in five gynecologic cancer patients reported losing health insurance for at least 1 month every year, and more than one in four reported having catastrophic health expenses annually.
Benjamin Albright, MD, of Duke University Medical Center in Durham, N.C., presented these results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10303).
“We found gynecologic cancer patients to have high rates of insurance churn and catastrophic health expenditures, particularly among the poor,” Dr. Albright said. “Traditional static measurements clearly underestimate the impact of uninsurance, with over 20% of patients reporting some period of uninsurance annually.”
There was no evidence of improvement in any outcome after the implementation of the ACA, compared with the pre-ACA period, “though our assessment was limited in estimate precision by small sample size,” Dr. Albright acknowledged.
Dynamic, not static
Oncology researchers who study access to care and financial toxicities often consider insurance status as a static characteristic, but in the U.S. health care system, the reality is quite different, with insurance status fluctuating by employment or ability to pay, sometimes on a month-to-month basis, according to Dr. Albright.
Citing the Commonwealth Fund’s definition of catastrophic health expenditures as “spending over 10% of income on health care,” Dr. Albright noted that the prevalence of catastrophic out-of-pocket costs “is also relatively poorly described among cancer patients, particularly in accounting for family spending and income dynamics.
“The Affordable Care Act contained measures to address both of these concerns, including coverage protections and expansions, and spending regulations,” he said.
Dr. Albright and colleagues at Duke and Memorial Sloan Kettering Cancer Center in New York assessed insurance churn and catastrophic health expenditures among gynecologic cancer patients, attempting to determine whether the ACA had helped to limit insurance churn and keep costs manageable.
Representative sample
The investigators conducted a retrospective study of data from Medical Expenditure Panel Survey respondents from 2006 through 2017, a period that spanned the implementation of the ACA in 2010.
The sample included 684 women younger than 65 years reporting care in the given year related to a gynecologic cancer diagnosis. The civilian, noninstitutionalized sample was weighted to represent an estimated average annual population of 533,000 persons. The population was majority White (87%) and non-Hispanic (85.5%).
The investigators found that, compared with the overall U.S. population of people under 65, gynecologic cancer patients were more likely to have incomes of 250% or less of the federal poverty line (45.1% vs. 32.2%, P < .001).
The cancer patients were more likely than was the general population to have less than full-time employment, with 15.2% and 10.5%, respectively, reporting a job change or job loss; 55.3% and 44.1%, respectively, being employed only part of a given year; and 38.6% and 32.4%, respectively, being unemployed for a full year (P < .05 for each comparison).
Gynecologic cancer patients continued to experience insurance troubles and financial hardships after the ACA went into effect, with 8.8% reporting loss of insurance, 18.7% reporting a change in insurance, 21.7% being uninsured for at least 1 month, and 8.4% being uninsured for an entire year.
In addition, 12.8% of gynecologic cancer patients reported catastrophic health expenditures in out-of-pocket costs alone, and 28.0% spent more than 10% of their income on health care when the cost of premiums was factored in.
The numbers were even worse for non-White and Hispanic patients, with 25.9% reporting an insurance change (vs. 16.3% for non-Hispanic Whites) and 30.2% reporting a period of not being insured (vs. 18.7% for non-Hispanic Whites). There were no differences in catastrophic health expenditures by race/ethnicity, however.
Not surprisingly, patients from low-income families had significantly higher probability of having catastrophic expenditures, at 22.7% vs. 3.0% for higher-income families for out-of-pocket expenses alone (P < .001), and 35.3% vs. 20.8%, respectively, when the cost of premiums was included (P = .01).
On the other hand, patients with full-year Medicaid coverage were less likely to suffer from catastrophic costs than were privately-insured patients, at 15.3% vs. 31.3% in the overall sample (P = .02), and 11.5% vs. 62.1% of low-income vs. higher-income patients (P < .001).
There was a trend toward lower catastrophic health expenditures among low-income patients after full implementation of the ACA – 2014-2017 – compared with 2006-2009, but this difference was not statistically significant.
How to change it
In a panel discussion following the presentation, comoderator Eloise Chapman-Davis, MD, of Weill Cornell Medicine in New York, said to Dr. Albright, “As we look to improve equity within our subspecialty, I would like to ask you to comment on how you believe your abstract will inform our gyn-oncology culture and speak to what changes that you believe are needed to better advocate for our patients.”
“I think that our abstract really shows the prevalence of the problems of financial toxicity and of instability in the insurance market in the U.S.,” he replied. “I think it points out that we need to be more proactive about identifying patients and seeking out patients who may be having issues related to financial toxicity, to try to refer people to resources sooner and upfront.”
The investigators did not list a funding source for the study. Dr. Albright and Dr. Chapman-Davis reported having no conflicts of interest.
A retrospective study of respondents to the Medical Expenditure Panel Survey showed that more than one in five gynecologic cancer patients reported losing health insurance for at least 1 month every year, and more than one in four reported having catastrophic health expenses annually.
Benjamin Albright, MD, of Duke University Medical Center in Durham, N.C., presented these results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10303).
“We found gynecologic cancer patients to have high rates of insurance churn and catastrophic health expenditures, particularly among the poor,” Dr. Albright said. “Traditional static measurements clearly underestimate the impact of uninsurance, with over 20% of patients reporting some period of uninsurance annually.”
There was no evidence of improvement in any outcome after the implementation of the ACA, compared with the pre-ACA period, “though our assessment was limited in estimate precision by small sample size,” Dr. Albright acknowledged.
Dynamic, not static
Oncology researchers who study access to care and financial toxicities often consider insurance status as a static characteristic, but in the U.S. health care system, the reality is quite different, with insurance status fluctuating by employment or ability to pay, sometimes on a month-to-month basis, according to Dr. Albright.
Citing the Commonwealth Fund’s definition of catastrophic health expenditures as “spending over 10% of income on health care,” Dr. Albright noted that the prevalence of catastrophic out-of-pocket costs “is also relatively poorly described among cancer patients, particularly in accounting for family spending and income dynamics.
“The Affordable Care Act contained measures to address both of these concerns, including coverage protections and expansions, and spending regulations,” he said.
Dr. Albright and colleagues at Duke and Memorial Sloan Kettering Cancer Center in New York assessed insurance churn and catastrophic health expenditures among gynecologic cancer patients, attempting to determine whether the ACA had helped to limit insurance churn and keep costs manageable.
Representative sample
The investigators conducted a retrospective study of data from Medical Expenditure Panel Survey respondents from 2006 through 2017, a period that spanned the implementation of the ACA in 2010.
The sample included 684 women younger than 65 years reporting care in the given year related to a gynecologic cancer diagnosis. The civilian, noninstitutionalized sample was weighted to represent an estimated average annual population of 533,000 persons. The population was majority White (87%) and non-Hispanic (85.5%).
The investigators found that, compared with the overall U.S. population of people under 65, gynecologic cancer patients were more likely to have incomes of 250% or less of the federal poverty line (45.1% vs. 32.2%, P < .001).
The cancer patients were more likely than was the general population to have less than full-time employment, with 15.2% and 10.5%, respectively, reporting a job change or job loss; 55.3% and 44.1%, respectively, being employed only part of a given year; and 38.6% and 32.4%, respectively, being unemployed for a full year (P < .05 for each comparison).
Gynecologic cancer patients continued to experience insurance troubles and financial hardships after the ACA went into effect, with 8.8% reporting loss of insurance, 18.7% reporting a change in insurance, 21.7% being uninsured for at least 1 month, and 8.4% being uninsured for an entire year.
In addition, 12.8% of gynecologic cancer patients reported catastrophic health expenditures in out-of-pocket costs alone, and 28.0% spent more than 10% of their income on health care when the cost of premiums was factored in.
The numbers were even worse for non-White and Hispanic patients, with 25.9% reporting an insurance change (vs. 16.3% for non-Hispanic Whites) and 30.2% reporting a period of not being insured (vs. 18.7% for non-Hispanic Whites). There were no differences in catastrophic health expenditures by race/ethnicity, however.
Not surprisingly, patients from low-income families had significantly higher probability of having catastrophic expenditures, at 22.7% vs. 3.0% for higher-income families for out-of-pocket expenses alone (P < .001), and 35.3% vs. 20.8%, respectively, when the cost of premiums was included (P = .01).
On the other hand, patients with full-year Medicaid coverage were less likely to suffer from catastrophic costs than were privately-insured patients, at 15.3% vs. 31.3% in the overall sample (P = .02), and 11.5% vs. 62.1% of low-income vs. higher-income patients (P < .001).
There was a trend toward lower catastrophic health expenditures among low-income patients after full implementation of the ACA – 2014-2017 – compared with 2006-2009, but this difference was not statistically significant.
How to change it
In a panel discussion following the presentation, comoderator Eloise Chapman-Davis, MD, of Weill Cornell Medicine in New York, said to Dr. Albright, “As we look to improve equity within our subspecialty, I would like to ask you to comment on how you believe your abstract will inform our gyn-oncology culture and speak to what changes that you believe are needed to better advocate for our patients.”
“I think that our abstract really shows the prevalence of the problems of financial toxicity and of instability in the insurance market in the U.S.,” he replied. “I think it points out that we need to be more proactive about identifying patients and seeking out patients who may be having issues related to financial toxicity, to try to refer people to resources sooner and upfront.”
The investigators did not list a funding source for the study. Dr. Albright and Dr. Chapman-Davis reported having no conflicts of interest.
A retrospective study of respondents to the Medical Expenditure Panel Survey showed that more than one in five gynecologic cancer patients reported losing health insurance for at least 1 month every year, and more than one in four reported having catastrophic health expenses annually.
Benjamin Albright, MD, of Duke University Medical Center in Durham, N.C., presented these results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10303).
“We found gynecologic cancer patients to have high rates of insurance churn and catastrophic health expenditures, particularly among the poor,” Dr. Albright said. “Traditional static measurements clearly underestimate the impact of uninsurance, with over 20% of patients reporting some period of uninsurance annually.”
There was no evidence of improvement in any outcome after the implementation of the ACA, compared with the pre-ACA period, “though our assessment was limited in estimate precision by small sample size,” Dr. Albright acknowledged.
Dynamic, not static
Oncology researchers who study access to care and financial toxicities often consider insurance status as a static characteristic, but in the U.S. health care system, the reality is quite different, with insurance status fluctuating by employment or ability to pay, sometimes on a month-to-month basis, according to Dr. Albright.
Citing the Commonwealth Fund’s definition of catastrophic health expenditures as “spending over 10% of income on health care,” Dr. Albright noted that the prevalence of catastrophic out-of-pocket costs “is also relatively poorly described among cancer patients, particularly in accounting for family spending and income dynamics.
“The Affordable Care Act contained measures to address both of these concerns, including coverage protections and expansions, and spending regulations,” he said.
Dr. Albright and colleagues at Duke and Memorial Sloan Kettering Cancer Center in New York assessed insurance churn and catastrophic health expenditures among gynecologic cancer patients, attempting to determine whether the ACA had helped to limit insurance churn and keep costs manageable.
Representative sample
The investigators conducted a retrospective study of data from Medical Expenditure Panel Survey respondents from 2006 through 2017, a period that spanned the implementation of the ACA in 2010.
The sample included 684 women younger than 65 years reporting care in the given year related to a gynecologic cancer diagnosis. The civilian, noninstitutionalized sample was weighted to represent an estimated average annual population of 533,000 persons. The population was majority White (87%) and non-Hispanic (85.5%).
The investigators found that, compared with the overall U.S. population of people under 65, gynecologic cancer patients were more likely to have incomes of 250% or less of the federal poverty line (45.1% vs. 32.2%, P < .001).
The cancer patients were more likely than was the general population to have less than full-time employment, with 15.2% and 10.5%, respectively, reporting a job change or job loss; 55.3% and 44.1%, respectively, being employed only part of a given year; and 38.6% and 32.4%, respectively, being unemployed for a full year (P < .05 for each comparison).
Gynecologic cancer patients continued to experience insurance troubles and financial hardships after the ACA went into effect, with 8.8% reporting loss of insurance, 18.7% reporting a change in insurance, 21.7% being uninsured for at least 1 month, and 8.4% being uninsured for an entire year.
In addition, 12.8% of gynecologic cancer patients reported catastrophic health expenditures in out-of-pocket costs alone, and 28.0% spent more than 10% of their income on health care when the cost of premiums was factored in.
The numbers were even worse for non-White and Hispanic patients, with 25.9% reporting an insurance change (vs. 16.3% for non-Hispanic Whites) and 30.2% reporting a period of not being insured (vs. 18.7% for non-Hispanic Whites). There were no differences in catastrophic health expenditures by race/ethnicity, however.
Not surprisingly, patients from low-income families had significantly higher probability of having catastrophic expenditures, at 22.7% vs. 3.0% for higher-income families for out-of-pocket expenses alone (P < .001), and 35.3% vs. 20.8%, respectively, when the cost of premiums was included (P = .01).
On the other hand, patients with full-year Medicaid coverage were less likely to suffer from catastrophic costs than were privately-insured patients, at 15.3% vs. 31.3% in the overall sample (P = .02), and 11.5% vs. 62.1% of low-income vs. higher-income patients (P < .001).
There was a trend toward lower catastrophic health expenditures among low-income patients after full implementation of the ACA – 2014-2017 – compared with 2006-2009, but this difference was not statistically significant.
How to change it
In a panel discussion following the presentation, comoderator Eloise Chapman-Davis, MD, of Weill Cornell Medicine in New York, said to Dr. Albright, “As we look to improve equity within our subspecialty, I would like to ask you to comment on how you believe your abstract will inform our gyn-oncology culture and speak to what changes that you believe are needed to better advocate for our patients.”
“I think that our abstract really shows the prevalence of the problems of financial toxicity and of instability in the insurance market in the U.S.,” he replied. “I think it points out that we need to be more proactive about identifying patients and seeking out patients who may be having issues related to financial toxicity, to try to refer people to resources sooner and upfront.”
The investigators did not list a funding source for the study. Dr. Albright and Dr. Chapman-Davis reported having no conflicts of interest.
FROM SGO 2021
Frail status may be better than age for predicting ovarian cancer outcomes
Baseball great Satchel Paige’s famous adage, “Age is a case of mind over matter. If you don’t mind, it don’t matter,” may also apply to candidates for ovarian cancer surgery. That’s because investigators have found that physical frailty is a better determinant of fitness for surgery than is calendar age.
Investigators conducted a retrospective analysis of 591 patients considered for primary resection of stage II to IV high-grade ovarian, fallopian tube, or peritoneal cancer. Results showed that a 10-item modified frailty index was better than patient age for predicting survival outcomes.
“Frailty does seem to correlate with age and increase with age, but it is not synonymous with age,” said investigator Katelyn F. Handley, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Frailty is a spectrum, and we can see patients of the same chronological age, but one may be a 76-year-old, ultra-distance triathlete, while another is in failing health and diminishing function,” Dr. Handley said at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10463).
Dr. Handley cited a consensus definition of frailty, published in 2013, as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”
Ten-item score
To assess the effect of frailty in ovarian cancer patients on surgical procedures and outcomes, the investigators retrospectively applied a modified frailty index (mFI) to patients who were treated at MD Anderson Cancer Center from April 2013 through September 2017.
The index is a sum of 10 items: Chronic obstructive pulmonary disease or recent pneumonia, heart failure, myocardial infarction, coronary artery disease, diabetes, hypertension, peripheral vascular disease, cerebrovascular disease, cerebrovascular accident with neurologic deficit, and poor Eastern Cooperative Oncology Group performance status (3 or 4).
Of the 591 patients who met inclusion criteria, 57% had mFI scores of 0, indicating no frailty, 29% had one frailty factor, and 14% had two or more factors.
Patient age did significantly correlate with mFI scores. Patients with an mFI score of 0 had a median age of 62 years, the median age in those with a score of 1 was 69 years, and the median age for those with scores of 2 or higher was 70.5 years (P <. 001).
Charlson comorbidity index scores also significantly increased with age, with mean scores of 3.00, 3.83, and 5.14 in patients with mFI scores of 0, 1, or 2, respectively (P <. 001).
“But if you look at the age ranges in each category, you’ll notice that there are patients as young as 47 with an mFI of greater than or equal to 2, and as old as 89 with an mFI of 0,” Dr. Handley pointed out.
Higher scores, fewer assessments
The investigators found that patients with suspected ovarian cancer with frailty scores of 2 or higher were less likely to be offered laparoscopic assessment to determine primary resectability than were those with scores of 1 or 0 (28% vs. 43% and 49%, respectively, P = .004).
Among all patients who underwent laparoscopic assessment, the predictive index score (modified Fagotti score) was more likely to be 8 or higher in patients with high frailty scores (58%, 48%, and 34% for scores of 2 or greater, 1, and 0, respectively; P = .038).
Only 17% of the most frail patients went on to primary debulking surgery, compared with 26% of patients with a single frailty factor and 34% of those with none (P = .015).
Patients with higher frailty scores were less likely to undergo primary or interval tumor reductive surgery (59% vs. 74% for those with mFI scores of 1 and 85% for those with scores of 0; P <. 001). The frailest patients were significantly more likely to undergo splenectomy (20%, 3%, and 6%, respectively; P = .001) and small bowel resection (14%, 8%, and 3%, respectively; P = .006).
Two-thirds of the most frail patients (64%) had postoperative complications, primarily gastrointestinal and renal complications, compared with 56% and 44% of patients with mFI scores of 1 or 0, respectively (P = .014).
Frailty was predictive of 30-day postoperative mortality (P = .005) but not postoperative length of stay.
Frailer patients were more likely to receive neoadjuvant chemotherapy (P = .033) but less likely to receive adjuvant chemotherapy (P <. 001).
mFI scores of 2 or greater and 1 were both associated with significantly worse progression-free survival (P < .001 and P = .022, respectively), but only an mFI of 2 or greater was associated with significantly worse overall survival (P <. 001).
On multivariate analysis controlling for frailty, age, stage, BRCA status, and tumor reductive surgery status, high frailty was associated with worse progression-free survival (P = .009) and a trend toward worse overall survival (P = .079).
High frailty was better than age for predicting worse progression-free survival (hazard ratio, 1.50; P = .017) and overall survival (HR, 1.57; P = .047)
Volume counts
In a separate presentation during the same session, Morcos Nakhla, of the University of California, Los Angeles, reported finding similar associations between frailty and worse surgical outcomes for ovarian cancer patients (Abstract 11016).
Mr. Nakhla and colleagues found that frail patients had a twofold increase in the risk of postoperative complications, a threefold increase in the risk for non-home dismissal, and a threefold increased risk of death (P <. 001 for all).
The team also found, however, that mortality improved from 2005 through 2017, despite an increase in frail patients over that time period.
In addition, higher surgical volumes were associated with decreased mortality among frail patients undergoing ovarian cancer surgery.
Navigating treatment
“Frailty syndrome is a medical syndrome. It’s not a disability,” said Jamie N. Bakkum-Gamez, MD, of the Mayo Clinic in Rochester, Minn., the invited discussant. “No patient or human wants to be frail, but at some point, we may all be at risk for frailty syndrome, and as we navigate much-needed novel ways to treat this medical syndrome, it’s imperative that we listen to the voice of the customer and that our communication and technology doesn’t add unanticipated stress.”
Dr. Bakkum-Gamez emphasized the importance of shared decision-making, screening for frailty syndrome, referral to higher volume surgical centers when practical, and surgical alternatives such as neoadjuvant chemotherapy with or without interval debulking surgery and palliative care.
Interventions for ameliorating frailty may include exercise, high-protein calorie supplementation, reduction of polypharmacy, and vitamin D supplementation.
“Sometimes, shared decision-making means deciding not to operate,” Dr. Bakkum-Gamez said. “This is sometimes amongst the hardest decisions for a surgeon. We know when we make the wrong decision in operating if our patient experiences a major, life-shortening complication, but it’s less clear to know if we make the wrong decision to not operate.”
The study by Dr. Handley and colleagues was funded by the Gulf Coast Consortia, MD Anderson, National Institutes of Health, American Cancer Society, and GOG Foundation. Mr. Nakhla and colleagues did not disclose a funding source. Dr. Handley, Mr. Nakhla, and Dr. Bakkum-Gamez all reported no relevant conflicts of interest.
Baseball great Satchel Paige’s famous adage, “Age is a case of mind over matter. If you don’t mind, it don’t matter,” may also apply to candidates for ovarian cancer surgery. That’s because investigators have found that physical frailty is a better determinant of fitness for surgery than is calendar age.
Investigators conducted a retrospective analysis of 591 patients considered for primary resection of stage II to IV high-grade ovarian, fallopian tube, or peritoneal cancer. Results showed that a 10-item modified frailty index was better than patient age for predicting survival outcomes.
“Frailty does seem to correlate with age and increase with age, but it is not synonymous with age,” said investigator Katelyn F. Handley, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Frailty is a spectrum, and we can see patients of the same chronological age, but one may be a 76-year-old, ultra-distance triathlete, while another is in failing health and diminishing function,” Dr. Handley said at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10463).
Dr. Handley cited a consensus definition of frailty, published in 2013, as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”
Ten-item score
To assess the effect of frailty in ovarian cancer patients on surgical procedures and outcomes, the investigators retrospectively applied a modified frailty index (mFI) to patients who were treated at MD Anderson Cancer Center from April 2013 through September 2017.
The index is a sum of 10 items: Chronic obstructive pulmonary disease or recent pneumonia, heart failure, myocardial infarction, coronary artery disease, diabetes, hypertension, peripheral vascular disease, cerebrovascular disease, cerebrovascular accident with neurologic deficit, and poor Eastern Cooperative Oncology Group performance status (3 or 4).
Of the 591 patients who met inclusion criteria, 57% had mFI scores of 0, indicating no frailty, 29% had one frailty factor, and 14% had two or more factors.
Patient age did significantly correlate with mFI scores. Patients with an mFI score of 0 had a median age of 62 years, the median age in those with a score of 1 was 69 years, and the median age for those with scores of 2 or higher was 70.5 years (P <. 001).
Charlson comorbidity index scores also significantly increased with age, with mean scores of 3.00, 3.83, and 5.14 in patients with mFI scores of 0, 1, or 2, respectively (P <. 001).
“But if you look at the age ranges in each category, you’ll notice that there are patients as young as 47 with an mFI of greater than or equal to 2, and as old as 89 with an mFI of 0,” Dr. Handley pointed out.
Higher scores, fewer assessments
The investigators found that patients with suspected ovarian cancer with frailty scores of 2 or higher were less likely to be offered laparoscopic assessment to determine primary resectability than were those with scores of 1 or 0 (28% vs. 43% and 49%, respectively, P = .004).
Among all patients who underwent laparoscopic assessment, the predictive index score (modified Fagotti score) was more likely to be 8 or higher in patients with high frailty scores (58%, 48%, and 34% for scores of 2 or greater, 1, and 0, respectively; P = .038).
Only 17% of the most frail patients went on to primary debulking surgery, compared with 26% of patients with a single frailty factor and 34% of those with none (P = .015).
Patients with higher frailty scores were less likely to undergo primary or interval tumor reductive surgery (59% vs. 74% for those with mFI scores of 1 and 85% for those with scores of 0; P <. 001). The frailest patients were significantly more likely to undergo splenectomy (20%, 3%, and 6%, respectively; P = .001) and small bowel resection (14%, 8%, and 3%, respectively; P = .006).
Two-thirds of the most frail patients (64%) had postoperative complications, primarily gastrointestinal and renal complications, compared with 56% and 44% of patients with mFI scores of 1 or 0, respectively (P = .014).
Frailty was predictive of 30-day postoperative mortality (P = .005) but not postoperative length of stay.
Frailer patients were more likely to receive neoadjuvant chemotherapy (P = .033) but less likely to receive adjuvant chemotherapy (P <. 001).
mFI scores of 2 or greater and 1 were both associated with significantly worse progression-free survival (P < .001 and P = .022, respectively), but only an mFI of 2 or greater was associated with significantly worse overall survival (P <. 001).
On multivariate analysis controlling for frailty, age, stage, BRCA status, and tumor reductive surgery status, high frailty was associated with worse progression-free survival (P = .009) and a trend toward worse overall survival (P = .079).
High frailty was better than age for predicting worse progression-free survival (hazard ratio, 1.50; P = .017) and overall survival (HR, 1.57; P = .047)
Volume counts
In a separate presentation during the same session, Morcos Nakhla, of the University of California, Los Angeles, reported finding similar associations between frailty and worse surgical outcomes for ovarian cancer patients (Abstract 11016).
Mr. Nakhla and colleagues found that frail patients had a twofold increase in the risk of postoperative complications, a threefold increase in the risk for non-home dismissal, and a threefold increased risk of death (P <. 001 for all).
The team also found, however, that mortality improved from 2005 through 2017, despite an increase in frail patients over that time period.
In addition, higher surgical volumes were associated with decreased mortality among frail patients undergoing ovarian cancer surgery.
Navigating treatment
“Frailty syndrome is a medical syndrome. It’s not a disability,” said Jamie N. Bakkum-Gamez, MD, of the Mayo Clinic in Rochester, Minn., the invited discussant. “No patient or human wants to be frail, but at some point, we may all be at risk for frailty syndrome, and as we navigate much-needed novel ways to treat this medical syndrome, it’s imperative that we listen to the voice of the customer and that our communication and technology doesn’t add unanticipated stress.”
Dr. Bakkum-Gamez emphasized the importance of shared decision-making, screening for frailty syndrome, referral to higher volume surgical centers when practical, and surgical alternatives such as neoadjuvant chemotherapy with or without interval debulking surgery and palliative care.
Interventions for ameliorating frailty may include exercise, high-protein calorie supplementation, reduction of polypharmacy, and vitamin D supplementation.
“Sometimes, shared decision-making means deciding not to operate,” Dr. Bakkum-Gamez said. “This is sometimes amongst the hardest decisions for a surgeon. We know when we make the wrong decision in operating if our patient experiences a major, life-shortening complication, but it’s less clear to know if we make the wrong decision to not operate.”
The study by Dr. Handley and colleagues was funded by the Gulf Coast Consortia, MD Anderson, National Institutes of Health, American Cancer Society, and GOG Foundation. Mr. Nakhla and colleagues did not disclose a funding source. Dr. Handley, Mr. Nakhla, and Dr. Bakkum-Gamez all reported no relevant conflicts of interest.
Baseball great Satchel Paige’s famous adage, “Age is a case of mind over matter. If you don’t mind, it don’t matter,” may also apply to candidates for ovarian cancer surgery. That’s because investigators have found that physical frailty is a better determinant of fitness for surgery than is calendar age.
Investigators conducted a retrospective analysis of 591 patients considered for primary resection of stage II to IV high-grade ovarian, fallopian tube, or peritoneal cancer. Results showed that a 10-item modified frailty index was better than patient age for predicting survival outcomes.
“Frailty does seem to correlate with age and increase with age, but it is not synonymous with age,” said investigator Katelyn F. Handley, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Frailty is a spectrum, and we can see patients of the same chronological age, but one may be a 76-year-old, ultra-distance triathlete, while another is in failing health and diminishing function,” Dr. Handley said at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10463).
Dr. Handley cited a consensus definition of frailty, published in 2013, as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”
Ten-item score
To assess the effect of frailty in ovarian cancer patients on surgical procedures and outcomes, the investigators retrospectively applied a modified frailty index (mFI) to patients who were treated at MD Anderson Cancer Center from April 2013 through September 2017.
The index is a sum of 10 items: Chronic obstructive pulmonary disease or recent pneumonia, heart failure, myocardial infarction, coronary artery disease, diabetes, hypertension, peripheral vascular disease, cerebrovascular disease, cerebrovascular accident with neurologic deficit, and poor Eastern Cooperative Oncology Group performance status (3 or 4).
Of the 591 patients who met inclusion criteria, 57% had mFI scores of 0, indicating no frailty, 29% had one frailty factor, and 14% had two or more factors.
Patient age did significantly correlate with mFI scores. Patients with an mFI score of 0 had a median age of 62 years, the median age in those with a score of 1 was 69 years, and the median age for those with scores of 2 or higher was 70.5 years (P <. 001).
Charlson comorbidity index scores also significantly increased with age, with mean scores of 3.00, 3.83, and 5.14 in patients with mFI scores of 0, 1, or 2, respectively (P <. 001).
“But if you look at the age ranges in each category, you’ll notice that there are patients as young as 47 with an mFI of greater than or equal to 2, and as old as 89 with an mFI of 0,” Dr. Handley pointed out.
Higher scores, fewer assessments
The investigators found that patients with suspected ovarian cancer with frailty scores of 2 or higher were less likely to be offered laparoscopic assessment to determine primary resectability than were those with scores of 1 or 0 (28% vs. 43% and 49%, respectively, P = .004).
Among all patients who underwent laparoscopic assessment, the predictive index score (modified Fagotti score) was more likely to be 8 or higher in patients with high frailty scores (58%, 48%, and 34% for scores of 2 or greater, 1, and 0, respectively; P = .038).
Only 17% of the most frail patients went on to primary debulking surgery, compared with 26% of patients with a single frailty factor and 34% of those with none (P = .015).
Patients with higher frailty scores were less likely to undergo primary or interval tumor reductive surgery (59% vs. 74% for those with mFI scores of 1 and 85% for those with scores of 0; P <. 001). The frailest patients were significantly more likely to undergo splenectomy (20%, 3%, and 6%, respectively; P = .001) and small bowel resection (14%, 8%, and 3%, respectively; P = .006).
Two-thirds of the most frail patients (64%) had postoperative complications, primarily gastrointestinal and renal complications, compared with 56% and 44% of patients with mFI scores of 1 or 0, respectively (P = .014).
Frailty was predictive of 30-day postoperative mortality (P = .005) but not postoperative length of stay.
Frailer patients were more likely to receive neoadjuvant chemotherapy (P = .033) but less likely to receive adjuvant chemotherapy (P <. 001).
mFI scores of 2 or greater and 1 were both associated with significantly worse progression-free survival (P < .001 and P = .022, respectively), but only an mFI of 2 or greater was associated with significantly worse overall survival (P <. 001).
On multivariate analysis controlling for frailty, age, stage, BRCA status, and tumor reductive surgery status, high frailty was associated with worse progression-free survival (P = .009) and a trend toward worse overall survival (P = .079).
High frailty was better than age for predicting worse progression-free survival (hazard ratio, 1.50; P = .017) and overall survival (HR, 1.57; P = .047)
Volume counts
In a separate presentation during the same session, Morcos Nakhla, of the University of California, Los Angeles, reported finding similar associations between frailty and worse surgical outcomes for ovarian cancer patients (Abstract 11016).
Mr. Nakhla and colleagues found that frail patients had a twofold increase in the risk of postoperative complications, a threefold increase in the risk for non-home dismissal, and a threefold increased risk of death (P <. 001 for all).
The team also found, however, that mortality improved from 2005 through 2017, despite an increase in frail patients over that time period.
In addition, higher surgical volumes were associated with decreased mortality among frail patients undergoing ovarian cancer surgery.
Navigating treatment
“Frailty syndrome is a medical syndrome. It’s not a disability,” said Jamie N. Bakkum-Gamez, MD, of the Mayo Clinic in Rochester, Minn., the invited discussant. “No patient or human wants to be frail, but at some point, we may all be at risk for frailty syndrome, and as we navigate much-needed novel ways to treat this medical syndrome, it’s imperative that we listen to the voice of the customer and that our communication and technology doesn’t add unanticipated stress.”
Dr. Bakkum-Gamez emphasized the importance of shared decision-making, screening for frailty syndrome, referral to higher volume surgical centers when practical, and surgical alternatives such as neoadjuvant chemotherapy with or without interval debulking surgery and palliative care.
Interventions for ameliorating frailty may include exercise, high-protein calorie supplementation, reduction of polypharmacy, and vitamin D supplementation.
“Sometimes, shared decision-making means deciding not to operate,” Dr. Bakkum-Gamez said. “This is sometimes amongst the hardest decisions for a surgeon. We know when we make the wrong decision in operating if our patient experiences a major, life-shortening complication, but it’s less clear to know if we make the wrong decision to not operate.”
The study by Dr. Handley and colleagues was funded by the Gulf Coast Consortia, MD Anderson, National Institutes of Health, American Cancer Society, and GOG Foundation. Mr. Nakhla and colleagues did not disclose a funding source. Dr. Handley, Mr. Nakhla, and Dr. Bakkum-Gamez all reported no relevant conflicts of interest.
FROM SGO 2021
Cytoreduction in advanced ovarian cancer: ‘Keep the status quo’
A retrospective, case-control study showed that optimal cytoreductive surgery is an independent predictor of overall survival, even when controlling for response to chemotherapy.
The findings were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10243).
Response to platinum-based chemotherapy is the strongest predictor of overall survival in advanced ovarian cancer, noted Nicholas Cardillo, MD, a gynecologic oncology fellow at the University of Iowa, Iowa City, who presented the findings at the meeting.
In recent years, a poor response to chemotherapy has sometimes been used as justification to forgo cytoreduction, Dr. Cardillo added.
He and his colleagues looked into this issue because evidence to support the practice is lacking. With their study, the researchers found that optimal cytoreduction – removing all disease of 1 cm or more – improved survival regardless of the response to chemotherapy.
“My advice right now is that debulking surgery should still be attempted in all patients with ovarian cancer because, as far as we know right now, optimal cytoreduction will improve survival,” Dr. Cardillo said in an interview. “Basically, this study argues to keep the status quo, which is to perform surgery.”
The status quo might change with future research, Dr. Cardillo acknowledged, “but as of right now, we have no evidence to support not pursuing cytoreduction in these patients.”
Study details and results
The researchers analyzed data on 234 patients who responded to platinum-based chemotherapy – meaning they had no evidence of disease for at least 6 months afterward – and 98 patients who did not respond – meaning they progressed during therapy, had stable disease, did not respond completely, or had a progression-free survival duration of less than 6 months. Subjects had stage III or IV high-grade serous ovarian cancer.
About three-quarters of responders and 57% of nonresponders had optimal surgery. Only seven patients in each group had fewer than six cycles of chemotherapy.
The mean age was 59 years in the responder group and 62 years among nonresponders. Stage IV disease, including upper-abdominal and chest involvement, was more common in the nonresponder group.
The median overall survival was 44.8 months in the responder group and 18.1 months among nonresponders (P < .001). The median overall survival was 34.2 months among patients who underwent optimal surgery and 24.8 months among those who did not (P < .001).
Predictors of survival
A multivariate analysis showed that response to chemotherapy had the greatest effect on survival, with a hazard ratio of 0.27 (P < .001).
“The second most significant predictor of overall survival was receipt of neoadjuvant chemotherapy [HR, 2.84; P < .001], which is intuitive as that is typically a marker for worse disease burden,” Dr. Cardillo said.
“But most importantly for our question is that optimal surgery is an independent significant factor in overall survival, even when controlling for other significant risk factors, including whether or not a patient responds to chemotherapy. The hazard ratio is 0.73 [P = .023], indicating a 25%-30% improvement in overall survival,” he added.
Based on these results, “surgical debulking should still be considered a component of the treatment algorithm in ovarian cancer patients who have a poor response to chemotherapy, if an optimal surgery is deemed feasible,” Dr. Cardillo concluded.
There was no funding for this study, and the investigators had no relevant disclosures.
A retrospective, case-control study showed that optimal cytoreductive surgery is an independent predictor of overall survival, even when controlling for response to chemotherapy.
The findings were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10243).
Response to platinum-based chemotherapy is the strongest predictor of overall survival in advanced ovarian cancer, noted Nicholas Cardillo, MD, a gynecologic oncology fellow at the University of Iowa, Iowa City, who presented the findings at the meeting.
In recent years, a poor response to chemotherapy has sometimes been used as justification to forgo cytoreduction, Dr. Cardillo added.
He and his colleagues looked into this issue because evidence to support the practice is lacking. With their study, the researchers found that optimal cytoreduction – removing all disease of 1 cm or more – improved survival regardless of the response to chemotherapy.
“My advice right now is that debulking surgery should still be attempted in all patients with ovarian cancer because, as far as we know right now, optimal cytoreduction will improve survival,” Dr. Cardillo said in an interview. “Basically, this study argues to keep the status quo, which is to perform surgery.”
The status quo might change with future research, Dr. Cardillo acknowledged, “but as of right now, we have no evidence to support not pursuing cytoreduction in these patients.”
Study details and results
The researchers analyzed data on 234 patients who responded to platinum-based chemotherapy – meaning they had no evidence of disease for at least 6 months afterward – and 98 patients who did not respond – meaning they progressed during therapy, had stable disease, did not respond completely, or had a progression-free survival duration of less than 6 months. Subjects had stage III or IV high-grade serous ovarian cancer.
About three-quarters of responders and 57% of nonresponders had optimal surgery. Only seven patients in each group had fewer than six cycles of chemotherapy.
The mean age was 59 years in the responder group and 62 years among nonresponders. Stage IV disease, including upper-abdominal and chest involvement, was more common in the nonresponder group.
The median overall survival was 44.8 months in the responder group and 18.1 months among nonresponders (P < .001). The median overall survival was 34.2 months among patients who underwent optimal surgery and 24.8 months among those who did not (P < .001).
Predictors of survival
A multivariate analysis showed that response to chemotherapy had the greatest effect on survival, with a hazard ratio of 0.27 (P < .001).
“The second most significant predictor of overall survival was receipt of neoadjuvant chemotherapy [HR, 2.84; P < .001], which is intuitive as that is typically a marker for worse disease burden,” Dr. Cardillo said.
“But most importantly for our question is that optimal surgery is an independent significant factor in overall survival, even when controlling for other significant risk factors, including whether or not a patient responds to chemotherapy. The hazard ratio is 0.73 [P = .023], indicating a 25%-30% improvement in overall survival,” he added.
Based on these results, “surgical debulking should still be considered a component of the treatment algorithm in ovarian cancer patients who have a poor response to chemotherapy, if an optimal surgery is deemed feasible,” Dr. Cardillo concluded.
There was no funding for this study, and the investigators had no relevant disclosures.
A retrospective, case-control study showed that optimal cytoreductive surgery is an independent predictor of overall survival, even when controlling for response to chemotherapy.
The findings were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10243).
Response to platinum-based chemotherapy is the strongest predictor of overall survival in advanced ovarian cancer, noted Nicholas Cardillo, MD, a gynecologic oncology fellow at the University of Iowa, Iowa City, who presented the findings at the meeting.
In recent years, a poor response to chemotherapy has sometimes been used as justification to forgo cytoreduction, Dr. Cardillo added.
He and his colleagues looked into this issue because evidence to support the practice is lacking. With their study, the researchers found that optimal cytoreduction – removing all disease of 1 cm or more – improved survival regardless of the response to chemotherapy.
“My advice right now is that debulking surgery should still be attempted in all patients with ovarian cancer because, as far as we know right now, optimal cytoreduction will improve survival,” Dr. Cardillo said in an interview. “Basically, this study argues to keep the status quo, which is to perform surgery.”
The status quo might change with future research, Dr. Cardillo acknowledged, “but as of right now, we have no evidence to support not pursuing cytoreduction in these patients.”
Study details and results
The researchers analyzed data on 234 patients who responded to platinum-based chemotherapy – meaning they had no evidence of disease for at least 6 months afterward – and 98 patients who did not respond – meaning they progressed during therapy, had stable disease, did not respond completely, or had a progression-free survival duration of less than 6 months. Subjects had stage III or IV high-grade serous ovarian cancer.
About three-quarters of responders and 57% of nonresponders had optimal surgery. Only seven patients in each group had fewer than six cycles of chemotherapy.
The mean age was 59 years in the responder group and 62 years among nonresponders. Stage IV disease, including upper-abdominal and chest involvement, was more common in the nonresponder group.
The median overall survival was 44.8 months in the responder group and 18.1 months among nonresponders (P < .001). The median overall survival was 34.2 months among patients who underwent optimal surgery and 24.8 months among those who did not (P < .001).
Predictors of survival
A multivariate analysis showed that response to chemotherapy had the greatest effect on survival, with a hazard ratio of 0.27 (P < .001).
“The second most significant predictor of overall survival was receipt of neoadjuvant chemotherapy [HR, 2.84; P < .001], which is intuitive as that is typically a marker for worse disease burden,” Dr. Cardillo said.
“But most importantly for our question is that optimal surgery is an independent significant factor in overall survival, even when controlling for other significant risk factors, including whether or not a patient responds to chemotherapy. The hazard ratio is 0.73 [P = .023], indicating a 25%-30% improvement in overall survival,” he added.
Based on these results, “surgical debulking should still be considered a component of the treatment algorithm in ovarian cancer patients who have a poor response to chemotherapy, if an optimal surgery is deemed feasible,” Dr. Cardillo concluded.
There was no funding for this study, and the investigators had no relevant disclosures.
FROM SGO 2021
Study: Gynecologic cancer therapy does not increase COVID-19 risks
Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.
The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.
Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.
Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.
With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.
Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
Study results
Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.
Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.
Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).
An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.
Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
More research needed
The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”
The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.
“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”
The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.
However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.
Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.
This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.
Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.
The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.
Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.
Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.
With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.
Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
Study results
Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.
Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.
Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).
An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.
Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
More research needed
The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”
The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.
“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”
The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.
However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.
Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.
This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.
Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.
The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.
Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.
Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.
With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.
Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
Study results
Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.
Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.
Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).
An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.
Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
More research needed
The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”
The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.
“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”
The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.
However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.
Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.
This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.
FROM SGO 2021
Intervention reduced racial disparities among patients in cancer trials
, according to researchers.
The team found that progression-free survival (PFS) was significantly worse for Black versus White women with endometrial cancer who were treated at the center between 2012 and 2018. However, PFS outcomes were similar for both races among patients from the center who were enrolled in clinical trials during the same period, after the center introduced a navigation program designed to reduce racial disparities.
The findings demonstrate that health care inequities can be overcome with specific interventions aimed at improving care for Black women, said Nathaniel L. Jones, MD of the Mitchell Cancer Institute at the University of South Alabama in Mobile.
Dr. Jones presented the findings at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10910).
Rationale: Building trust, providing equitable care
Black women comprise 7% of endometrial cancer diagnoses across the United States but account for 15% of all deaths, Dr. Jones noted. Compared with White women, Black women are up to 80% more likely to die from endometrial cancer.
“Perhaps even more concerning is that endometrial cancer is one of few cancers with increasing incidence and mortality, which further exacerbates the disparities,” Dr. Jones said.
In the Deep South, which carries “an unequal burden” of endometrial cancer incidence and mortality compared with the rest of the United States, multiple additional barriers exist that further exacerbate health care inequities, Dr. Jones said.
The barriers include greater poverty, mortality, social and economic disadvantages, and mistrust in “the medical establishment” among Black patients.
“The onus is on us as providers to provide an approach to cancer care that allows our patients to trust us and provide equitable cancer care for the women we serve,” Dr. Jones said. “To that end, we sought to investigate clinical trial enrollment at our institution after the implementation of patient-based programs designed specifically to enhance minority enrollment in clinical trials. We then evaluated the impact of clinical trial enrollment and race on survival.”
A ‘multifaceted’ intervention
“An intentional, multifaceted intervention was created to address Black patient enrollment onto clinical trials,” Dr. Jones explained.
His center implemented a lay navigation program to increase trial awareness and participation among minorities, help patients understand the risks and benefits of clinical trial participation, and help patients and their families navigate the enrollment and participation processes.
Under the program, all new endometrial cancer patients were assigned a lay navigator. The program included an education component to inform patients of the risks and benefits of clinical trial participation.
Another aspect was hiring a “diverse lay navigation workforce ... that mirrored the demographics of our catchment area,” which has more than double the minority population, compared with the national average, Dr. Jones noted.
Results: Improved PFS
To evaluate the efficacy of their intervention, the researchers conducted a retrospective review of 1,021 patients with endometrial cancer treated at Mitchell Cancer Institute between 2012 and 2018. There were 277 Black women and 718 White women in the overall cohort, and 23 Black women and 61 White women were enrolled in clinical trials.
After accounting for age-adjusted endometrial cancer incidence in the United States, the observed trial enrollment of Black women was statistically similar to expected enrollment (1.03-fold lower than expected). Compared with regional “Deep South” data, however, enrollment was 1.15-fold higher than expected for Black patients, Dr. Jones said.
Among all women with endometrial cancer treated at the Mitchell Cancer Institute, the median PFS was 14 months in Black women and 20 months in White women (P = .002). Among patients enrolled in clinical trials, however, the median PFS was 13 months for Black women and 14 months for White women (P = .280).
In the entire cohort, Black women had more aggressive histology, more advanced-stage disease, and a higher proportion of Medicaid or self-pay status. Among those enrolled in clinical trials, there was no difference between races in stage, grade, histology, insurance, or performance status.
The findings show that inequities in clinical trial enrollment can be overcome, and patient-based interventions can be helpful in improving enrollment of minority women, Dr. Jones concluded.
Doing better, starting small
Invited discussant Kemi M. Doll, MD, commended Dr. Jones and his colleagues for their “incredible, intervention-focused work,” but she asked: “Is this good enough?”
Analyses are needed to understand what drove the differences among trial participants versus the overall population, said Dr. Doll, a gynecologic oncologist at the University of Washington in Seattle.
For example, determining whether outcomes in the trial participants were driven by better PFS among Black women or worse PFS among White women could “help to identify next steps,” Dr. Doll said.
She stressed that “everyone” can engage in local-level efforts to improve trial enrollment, equity, and outcomes.
“A powerful mantra I was exposed to several years ago regarding equity is, ‘Here. Now. Small. Doable.’ We are often paralyzed by the long-standing and deeply embedded inequities in our health care system, but we can choose to move into action by following ‘Here. Now. Small. Doable,’” Dr. Doll said. “It reminds us to start where we are..., to start now, and stop waiting for convenience because equity work is not convenient.”
The key is recognizing individual power to enact change and focusing on “what we can change and not what we can’t,” she said.
Tools are available on the national level to help facilitate clinical trial enrollment of historically excluded populations, Dr. Doll added.
She cited a report outlining strategies for accruing diverse populations in clinical trials at eight U.S. cancer centers. The report addresses development of community partnerships and community advisory boards, training in culturally competent and congruent trial design, use of lay navigation, the importance of balancing benefits of participation with patient time and risk, and invoking a sense of altruism for family and community, Dr. Doll said.
“Baking these into trial design and recruitment are known, evidence-based methods to improve enrollment of [minority] populations,” she said. “Deciding to make these design elements mandatory for trials to be approved and executed is the kind of paradigm-shifting action that is available to us now.”
Dr. Jones and Dr. Doll both reported having no disclosures.
, according to researchers.
The team found that progression-free survival (PFS) was significantly worse for Black versus White women with endometrial cancer who were treated at the center between 2012 and 2018. However, PFS outcomes were similar for both races among patients from the center who were enrolled in clinical trials during the same period, after the center introduced a navigation program designed to reduce racial disparities.
The findings demonstrate that health care inequities can be overcome with specific interventions aimed at improving care for Black women, said Nathaniel L. Jones, MD of the Mitchell Cancer Institute at the University of South Alabama in Mobile.
Dr. Jones presented the findings at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10910).
Rationale: Building trust, providing equitable care
Black women comprise 7% of endometrial cancer diagnoses across the United States but account for 15% of all deaths, Dr. Jones noted. Compared with White women, Black women are up to 80% more likely to die from endometrial cancer.
“Perhaps even more concerning is that endometrial cancer is one of few cancers with increasing incidence and mortality, which further exacerbates the disparities,” Dr. Jones said.
In the Deep South, which carries “an unequal burden” of endometrial cancer incidence and mortality compared with the rest of the United States, multiple additional barriers exist that further exacerbate health care inequities, Dr. Jones said.
The barriers include greater poverty, mortality, social and economic disadvantages, and mistrust in “the medical establishment” among Black patients.
“The onus is on us as providers to provide an approach to cancer care that allows our patients to trust us and provide equitable cancer care for the women we serve,” Dr. Jones said. “To that end, we sought to investigate clinical trial enrollment at our institution after the implementation of patient-based programs designed specifically to enhance minority enrollment in clinical trials. We then evaluated the impact of clinical trial enrollment and race on survival.”
A ‘multifaceted’ intervention
“An intentional, multifaceted intervention was created to address Black patient enrollment onto clinical trials,” Dr. Jones explained.
His center implemented a lay navigation program to increase trial awareness and participation among minorities, help patients understand the risks and benefits of clinical trial participation, and help patients and their families navigate the enrollment and participation processes.
Under the program, all new endometrial cancer patients were assigned a lay navigator. The program included an education component to inform patients of the risks and benefits of clinical trial participation.
Another aspect was hiring a “diverse lay navigation workforce ... that mirrored the demographics of our catchment area,” which has more than double the minority population, compared with the national average, Dr. Jones noted.
Results: Improved PFS
To evaluate the efficacy of their intervention, the researchers conducted a retrospective review of 1,021 patients with endometrial cancer treated at Mitchell Cancer Institute between 2012 and 2018. There were 277 Black women and 718 White women in the overall cohort, and 23 Black women and 61 White women were enrolled in clinical trials.
After accounting for age-adjusted endometrial cancer incidence in the United States, the observed trial enrollment of Black women was statistically similar to expected enrollment (1.03-fold lower than expected). Compared with regional “Deep South” data, however, enrollment was 1.15-fold higher than expected for Black patients, Dr. Jones said.
Among all women with endometrial cancer treated at the Mitchell Cancer Institute, the median PFS was 14 months in Black women and 20 months in White women (P = .002). Among patients enrolled in clinical trials, however, the median PFS was 13 months for Black women and 14 months for White women (P = .280).
In the entire cohort, Black women had more aggressive histology, more advanced-stage disease, and a higher proportion of Medicaid or self-pay status. Among those enrolled in clinical trials, there was no difference between races in stage, grade, histology, insurance, or performance status.
The findings show that inequities in clinical trial enrollment can be overcome, and patient-based interventions can be helpful in improving enrollment of minority women, Dr. Jones concluded.
Doing better, starting small
Invited discussant Kemi M. Doll, MD, commended Dr. Jones and his colleagues for their “incredible, intervention-focused work,” but she asked: “Is this good enough?”
Analyses are needed to understand what drove the differences among trial participants versus the overall population, said Dr. Doll, a gynecologic oncologist at the University of Washington in Seattle.
For example, determining whether outcomes in the trial participants were driven by better PFS among Black women or worse PFS among White women could “help to identify next steps,” Dr. Doll said.
She stressed that “everyone” can engage in local-level efforts to improve trial enrollment, equity, and outcomes.
“A powerful mantra I was exposed to several years ago regarding equity is, ‘Here. Now. Small. Doable.’ We are often paralyzed by the long-standing and deeply embedded inequities in our health care system, but we can choose to move into action by following ‘Here. Now. Small. Doable,’” Dr. Doll said. “It reminds us to start where we are..., to start now, and stop waiting for convenience because equity work is not convenient.”
The key is recognizing individual power to enact change and focusing on “what we can change and not what we can’t,” she said.
Tools are available on the national level to help facilitate clinical trial enrollment of historically excluded populations, Dr. Doll added.
She cited a report outlining strategies for accruing diverse populations in clinical trials at eight U.S. cancer centers. The report addresses development of community partnerships and community advisory boards, training in culturally competent and congruent trial design, use of lay navigation, the importance of balancing benefits of participation with patient time and risk, and invoking a sense of altruism for family and community, Dr. Doll said.
“Baking these into trial design and recruitment are known, evidence-based methods to improve enrollment of [minority] populations,” she said. “Deciding to make these design elements mandatory for trials to be approved and executed is the kind of paradigm-shifting action that is available to us now.”
Dr. Jones and Dr. Doll both reported having no disclosures.
, according to researchers.
The team found that progression-free survival (PFS) was significantly worse for Black versus White women with endometrial cancer who were treated at the center between 2012 and 2018. However, PFS outcomes were similar for both races among patients from the center who were enrolled in clinical trials during the same period, after the center introduced a navigation program designed to reduce racial disparities.
The findings demonstrate that health care inequities can be overcome with specific interventions aimed at improving care for Black women, said Nathaniel L. Jones, MD of the Mitchell Cancer Institute at the University of South Alabama in Mobile.
Dr. Jones presented the findings at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10910).
Rationale: Building trust, providing equitable care
Black women comprise 7% of endometrial cancer diagnoses across the United States but account for 15% of all deaths, Dr. Jones noted. Compared with White women, Black women are up to 80% more likely to die from endometrial cancer.
“Perhaps even more concerning is that endometrial cancer is one of few cancers with increasing incidence and mortality, which further exacerbates the disparities,” Dr. Jones said.
In the Deep South, which carries “an unequal burden” of endometrial cancer incidence and mortality compared with the rest of the United States, multiple additional barriers exist that further exacerbate health care inequities, Dr. Jones said.
The barriers include greater poverty, mortality, social and economic disadvantages, and mistrust in “the medical establishment” among Black patients.
“The onus is on us as providers to provide an approach to cancer care that allows our patients to trust us and provide equitable cancer care for the women we serve,” Dr. Jones said. “To that end, we sought to investigate clinical trial enrollment at our institution after the implementation of patient-based programs designed specifically to enhance minority enrollment in clinical trials. We then evaluated the impact of clinical trial enrollment and race on survival.”
A ‘multifaceted’ intervention
“An intentional, multifaceted intervention was created to address Black patient enrollment onto clinical trials,” Dr. Jones explained.
His center implemented a lay navigation program to increase trial awareness and participation among minorities, help patients understand the risks and benefits of clinical trial participation, and help patients and their families navigate the enrollment and participation processes.
Under the program, all new endometrial cancer patients were assigned a lay navigator. The program included an education component to inform patients of the risks and benefits of clinical trial participation.
Another aspect was hiring a “diverse lay navigation workforce ... that mirrored the demographics of our catchment area,” which has more than double the minority population, compared with the national average, Dr. Jones noted.
Results: Improved PFS
To evaluate the efficacy of their intervention, the researchers conducted a retrospective review of 1,021 patients with endometrial cancer treated at Mitchell Cancer Institute between 2012 and 2018. There were 277 Black women and 718 White women in the overall cohort, and 23 Black women and 61 White women were enrolled in clinical trials.
After accounting for age-adjusted endometrial cancer incidence in the United States, the observed trial enrollment of Black women was statistically similar to expected enrollment (1.03-fold lower than expected). Compared with regional “Deep South” data, however, enrollment was 1.15-fold higher than expected for Black patients, Dr. Jones said.
Among all women with endometrial cancer treated at the Mitchell Cancer Institute, the median PFS was 14 months in Black women and 20 months in White women (P = .002). Among patients enrolled in clinical trials, however, the median PFS was 13 months for Black women and 14 months for White women (P = .280).
In the entire cohort, Black women had more aggressive histology, more advanced-stage disease, and a higher proportion of Medicaid or self-pay status. Among those enrolled in clinical trials, there was no difference between races in stage, grade, histology, insurance, or performance status.
The findings show that inequities in clinical trial enrollment can be overcome, and patient-based interventions can be helpful in improving enrollment of minority women, Dr. Jones concluded.
Doing better, starting small
Invited discussant Kemi M. Doll, MD, commended Dr. Jones and his colleagues for their “incredible, intervention-focused work,” but she asked: “Is this good enough?”
Analyses are needed to understand what drove the differences among trial participants versus the overall population, said Dr. Doll, a gynecologic oncologist at the University of Washington in Seattle.
For example, determining whether outcomes in the trial participants were driven by better PFS among Black women or worse PFS among White women could “help to identify next steps,” Dr. Doll said.
She stressed that “everyone” can engage in local-level efforts to improve trial enrollment, equity, and outcomes.
“A powerful mantra I was exposed to several years ago regarding equity is, ‘Here. Now. Small. Doable.’ We are often paralyzed by the long-standing and deeply embedded inequities in our health care system, but we can choose to move into action by following ‘Here. Now. Small. Doable,’” Dr. Doll said. “It reminds us to start where we are..., to start now, and stop waiting for convenience because equity work is not convenient.”
The key is recognizing individual power to enact change and focusing on “what we can change and not what we can’t,” she said.
Tools are available on the national level to help facilitate clinical trial enrollment of historically excluded populations, Dr. Doll added.
She cited a report outlining strategies for accruing diverse populations in clinical trials at eight U.S. cancer centers. The report addresses development of community partnerships and community advisory boards, training in culturally competent and congruent trial design, use of lay navigation, the importance of balancing benefits of participation with patient time and risk, and invoking a sense of altruism for family and community, Dr. Doll said.
“Baking these into trial design and recruitment are known, evidence-based methods to improve enrollment of [minority] populations,” she said. “Deciding to make these design elements mandatory for trials to be approved and executed is the kind of paradigm-shifting action that is available to us now.”
Dr. Jones and Dr. Doll both reported having no disclosures.
FROM SGO 2021