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TKI/BiTE combo extends survival of older patients with Ph+ALL
ATLANTA – Older patients with acute lymphoblastic leukemia positive for the Philadelphia chromosome (Ph+ALL) are often not fit enough to withstand intensive chemotherapy and stem cell transplants, but remissions with alternative therapies are usually short lived.
Now, results from an ongoing study suggest that the combination of the
The new results were reported by investigators in the SWOG Cancer Research Network and come from a cohort of 25 patients with a median age of 73 years with newly diagnosed Ph+ALL or ALL with dasatinib-sensitive fusions of mutations (Ph-like ALL).
Nearly all (23 of 25 patients, 92%) had complete remissions, and 5 of 16 patients for whom minimal residual disease (MRD) data were available were MRD negative at day 28, said Anjali Advani, MD, from the Cleveland Clinic.
At a median follow-up of 1.7 years, the estimated 3-year disease-free survival rate was 80%, and the estimated overall survival rate was 85%, the investigators reported in a poster presentation at the annual meeting of the American Society of Hematology.
“I think the biggest question will be longer-term follow-up. We clearly see high remission rates in this population, but the issue is whether in these elderly patients who are not candidates for chemo we can prolong remission by the addition of other treatments, such as blinatumomab,” she said in an interview with this news organization.
“The follow-up is reasonable at this point, and as we get longer follow-up, if the current 3-year survival estimates hold up, that would be very encouraging,” she said.
Early promise
A leukemia specialist who was not involved in the study told this news organization that the results are promising, but added that it’s too early to make definitive judgments about the efficacy of the combination.
“People have used just a tyrosine kinase inhibitor and prednisone in these patients and gotten remissions, but they just don’t last,” said Peter Emanuel, MD, from CHI St. Vincent Infirmary in Little Rock, Ark.
“The promise with this approach is that you’re getting a longer-lasting remission – maybe not a cure, but a longer-lasting remission – without having to use intensive chemotherapy,” he said.
“It’s still a pretty small study, so I think this is going to require a bigger trial, looking at more patients, but it’s certainly very encouraging and very promising,” he added.
Hanno Hock, MD, PhD, a leukemia researcher at the Mass General Cancer Center in Boston, said in an interview that “the whole idea here is to add this newer agent, blinatumomab, to make those good initial responses more durable, and it looks like it is able to do that with very impressive initial data,” he said.
“The caveat is that this is still early, and one needs to wait and see how it all pans out, but it’s very well tolerated, and definitely the next logical step in trying to offer something to people who cannot tolerate more aggressive therapy such as transplant,” Dr. Hock added.
Study results
The new results come from a feasibility cohort of patients enrolled in the SWOG S1318 trial, which studied blinatumomab plus chemotherapy and prednisone in older patients with Ph-ALL, as well as blinatumomab, dasatinib, and prednisone in older adults with Ph+ ALL.
Patients 65 and older with newly diagnosed or relapsed/refractory Ph+ALL or Ph-like ALL and no central nervous system disease were eligible for the arm of the trial described here. All patients with data reported in this analysis had newly diagnosed ALL.
Patients first received a single induction cycle of dasatinib and prednisone and were then evaluated for response. Patients with a complete remission (CR) or CR with incomplete recovery of blood counts (CRi) would then undergo prednisone tapering while continuing dasatinib until day 84. Patients without a CR or CRi at day 28 who had remissions by day 56 then also continued dasatinib until day 84.
Those patients still in remission at day 84 went on to three cycles of blinatumomab and dasatinib, followed by dasatinib and prednisone maintenance until unacceptable toxicity or disease progression. Patients may remain on maintenance for up to 10 years after registration.
Patients who do not have a CR or CRi by day 84 can receive reinduction with up to two total cycles of blinatumomab, with those who get a remission moving on to the blinatumomab/ dasatinib combination and those who do not going off protocol.
Of the 25 patients, 23 had a CR following dasatinib/prednisone induction. As noted, 5 of 16 patients evaluable for MRD were MRD negative.
Four patients did not receive postremission therapy, two because of adverse events, one who went on to transplant, and one because of insurance issues.
In a safety review early in the study, 4 of 12 evaluable patients were found to have dose-limiting toxicities, including one case each of grade 3 dyspnea and gastrointestinal pain (in a single patient), hypertension, dyspnea, and hyperglycemia.
These adverse events were deemed acceptable by both U.S. Food and Drug Administration and National Cancer Institute reviewers, and this arm of the study was allowed to continue, Dr. Advani noted.
The study was funded by grants from the National Institutes of Health. Dr. Advani disclosed financial relationships with several companies. Dr. Emanuel and Dr. Hock have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ATLANTA – Older patients with acute lymphoblastic leukemia positive for the Philadelphia chromosome (Ph+ALL) are often not fit enough to withstand intensive chemotherapy and stem cell transplants, but remissions with alternative therapies are usually short lived.
Now, results from an ongoing study suggest that the combination of the
The new results were reported by investigators in the SWOG Cancer Research Network and come from a cohort of 25 patients with a median age of 73 years with newly diagnosed Ph+ALL or ALL with dasatinib-sensitive fusions of mutations (Ph-like ALL).
Nearly all (23 of 25 patients, 92%) had complete remissions, and 5 of 16 patients for whom minimal residual disease (MRD) data were available were MRD negative at day 28, said Anjali Advani, MD, from the Cleveland Clinic.
At a median follow-up of 1.7 years, the estimated 3-year disease-free survival rate was 80%, and the estimated overall survival rate was 85%, the investigators reported in a poster presentation at the annual meeting of the American Society of Hematology.
“I think the biggest question will be longer-term follow-up. We clearly see high remission rates in this population, but the issue is whether in these elderly patients who are not candidates for chemo we can prolong remission by the addition of other treatments, such as blinatumomab,” she said in an interview with this news organization.
“The follow-up is reasonable at this point, and as we get longer follow-up, if the current 3-year survival estimates hold up, that would be very encouraging,” she said.
Early promise
A leukemia specialist who was not involved in the study told this news organization that the results are promising, but added that it’s too early to make definitive judgments about the efficacy of the combination.
“People have used just a tyrosine kinase inhibitor and prednisone in these patients and gotten remissions, but they just don’t last,” said Peter Emanuel, MD, from CHI St. Vincent Infirmary in Little Rock, Ark.
“The promise with this approach is that you’re getting a longer-lasting remission – maybe not a cure, but a longer-lasting remission – without having to use intensive chemotherapy,” he said.
“It’s still a pretty small study, so I think this is going to require a bigger trial, looking at more patients, but it’s certainly very encouraging and very promising,” he added.
Hanno Hock, MD, PhD, a leukemia researcher at the Mass General Cancer Center in Boston, said in an interview that “the whole idea here is to add this newer agent, blinatumomab, to make those good initial responses more durable, and it looks like it is able to do that with very impressive initial data,” he said.
“The caveat is that this is still early, and one needs to wait and see how it all pans out, but it’s very well tolerated, and definitely the next logical step in trying to offer something to people who cannot tolerate more aggressive therapy such as transplant,” Dr. Hock added.
Study results
The new results come from a feasibility cohort of patients enrolled in the SWOG S1318 trial, which studied blinatumomab plus chemotherapy and prednisone in older patients with Ph-ALL, as well as blinatumomab, dasatinib, and prednisone in older adults with Ph+ ALL.
Patients 65 and older with newly diagnosed or relapsed/refractory Ph+ALL or Ph-like ALL and no central nervous system disease were eligible for the arm of the trial described here. All patients with data reported in this analysis had newly diagnosed ALL.
Patients first received a single induction cycle of dasatinib and prednisone and were then evaluated for response. Patients with a complete remission (CR) or CR with incomplete recovery of blood counts (CRi) would then undergo prednisone tapering while continuing dasatinib until day 84. Patients without a CR or CRi at day 28 who had remissions by day 56 then also continued dasatinib until day 84.
Those patients still in remission at day 84 went on to three cycles of blinatumomab and dasatinib, followed by dasatinib and prednisone maintenance until unacceptable toxicity or disease progression. Patients may remain on maintenance for up to 10 years after registration.
Patients who do not have a CR or CRi by day 84 can receive reinduction with up to two total cycles of blinatumomab, with those who get a remission moving on to the blinatumomab/ dasatinib combination and those who do not going off protocol.
Of the 25 patients, 23 had a CR following dasatinib/prednisone induction. As noted, 5 of 16 patients evaluable for MRD were MRD negative.
Four patients did not receive postremission therapy, two because of adverse events, one who went on to transplant, and one because of insurance issues.
In a safety review early in the study, 4 of 12 evaluable patients were found to have dose-limiting toxicities, including one case each of grade 3 dyspnea and gastrointestinal pain (in a single patient), hypertension, dyspnea, and hyperglycemia.
These adverse events were deemed acceptable by both U.S. Food and Drug Administration and National Cancer Institute reviewers, and this arm of the study was allowed to continue, Dr. Advani noted.
The study was funded by grants from the National Institutes of Health. Dr. Advani disclosed financial relationships with several companies. Dr. Emanuel and Dr. Hock have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ATLANTA – Older patients with acute lymphoblastic leukemia positive for the Philadelphia chromosome (Ph+ALL) are often not fit enough to withstand intensive chemotherapy and stem cell transplants, but remissions with alternative therapies are usually short lived.
Now, results from an ongoing study suggest that the combination of the
The new results were reported by investigators in the SWOG Cancer Research Network and come from a cohort of 25 patients with a median age of 73 years with newly diagnosed Ph+ALL or ALL with dasatinib-sensitive fusions of mutations (Ph-like ALL).
Nearly all (23 of 25 patients, 92%) had complete remissions, and 5 of 16 patients for whom minimal residual disease (MRD) data were available were MRD negative at day 28, said Anjali Advani, MD, from the Cleveland Clinic.
At a median follow-up of 1.7 years, the estimated 3-year disease-free survival rate was 80%, and the estimated overall survival rate was 85%, the investigators reported in a poster presentation at the annual meeting of the American Society of Hematology.
“I think the biggest question will be longer-term follow-up. We clearly see high remission rates in this population, but the issue is whether in these elderly patients who are not candidates for chemo we can prolong remission by the addition of other treatments, such as blinatumomab,” she said in an interview with this news organization.
“The follow-up is reasonable at this point, and as we get longer follow-up, if the current 3-year survival estimates hold up, that would be very encouraging,” she said.
Early promise
A leukemia specialist who was not involved in the study told this news organization that the results are promising, but added that it’s too early to make definitive judgments about the efficacy of the combination.
“People have used just a tyrosine kinase inhibitor and prednisone in these patients and gotten remissions, but they just don’t last,” said Peter Emanuel, MD, from CHI St. Vincent Infirmary in Little Rock, Ark.
“The promise with this approach is that you’re getting a longer-lasting remission – maybe not a cure, but a longer-lasting remission – without having to use intensive chemotherapy,” he said.
“It’s still a pretty small study, so I think this is going to require a bigger trial, looking at more patients, but it’s certainly very encouraging and very promising,” he added.
Hanno Hock, MD, PhD, a leukemia researcher at the Mass General Cancer Center in Boston, said in an interview that “the whole idea here is to add this newer agent, blinatumomab, to make those good initial responses more durable, and it looks like it is able to do that with very impressive initial data,” he said.
“The caveat is that this is still early, and one needs to wait and see how it all pans out, but it’s very well tolerated, and definitely the next logical step in trying to offer something to people who cannot tolerate more aggressive therapy such as transplant,” Dr. Hock added.
Study results
The new results come from a feasibility cohort of patients enrolled in the SWOG S1318 trial, which studied blinatumomab plus chemotherapy and prednisone in older patients with Ph-ALL, as well as blinatumomab, dasatinib, and prednisone in older adults with Ph+ ALL.
Patients 65 and older with newly diagnosed or relapsed/refractory Ph+ALL or Ph-like ALL and no central nervous system disease were eligible for the arm of the trial described here. All patients with data reported in this analysis had newly diagnosed ALL.
Patients first received a single induction cycle of dasatinib and prednisone and were then evaluated for response. Patients with a complete remission (CR) or CR with incomplete recovery of blood counts (CRi) would then undergo prednisone tapering while continuing dasatinib until day 84. Patients without a CR or CRi at day 28 who had remissions by day 56 then also continued dasatinib until day 84.
Those patients still in remission at day 84 went on to three cycles of blinatumomab and dasatinib, followed by dasatinib and prednisone maintenance until unacceptable toxicity or disease progression. Patients may remain on maintenance for up to 10 years after registration.
Patients who do not have a CR or CRi by day 84 can receive reinduction with up to two total cycles of blinatumomab, with those who get a remission moving on to the blinatumomab/ dasatinib combination and those who do not going off protocol.
Of the 25 patients, 23 had a CR following dasatinib/prednisone induction. As noted, 5 of 16 patients evaluable for MRD were MRD negative.
Four patients did not receive postremission therapy, two because of adverse events, one who went on to transplant, and one because of insurance issues.
In a safety review early in the study, 4 of 12 evaluable patients were found to have dose-limiting toxicities, including one case each of grade 3 dyspnea and gastrointestinal pain (in a single patient), hypertension, dyspnea, and hyperglycemia.
These adverse events were deemed acceptable by both U.S. Food and Drug Administration and National Cancer Institute reviewers, and this arm of the study was allowed to continue, Dr. Advani noted.
The study was funded by grants from the National Institutes of Health. Dr. Advani disclosed financial relationships with several companies. Dr. Emanuel and Dr. Hock have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASH 2021
Louisiana to require the COVID-19 vaccine for students
Louisiana Gov. John Bel Edwards says the state government plans to make the COVID-19 vaccine a required immunization for students 16 and older in the state’s public school system.
“I just think it’s really, really important to embrace the science and really it’s also important to not engage in misinformation,” said Gov. Edwards, a Democrat, according to The Advocate. “Absent some compelling reason, which I at present have not seen, I fully expect that we will be adding the vaccine to the schedule.”
Parents could opt out their children from the requirement with a letter from a medical provider or a simple signature in dissent, The Advocate reported. The new rule would go into effect at the start of the 2022 school year and at first would apply to students aged 16 and older.
Republican legislators voiced their opposition to the COVID-19 vaccine requirement at a hearing on Dec. 6, calling it unneeded and an example of governmental overreach.
“I believe the vaccine should be highly recommended but not mandated,” state Rep. Laurie Schlegel said, according to TV station WDSU.
State Sen. Cameron Henry of Metairie said he received “hundreds of emails” from parents asking him to prevent the rule from going into effect, WDSU said.
WDSU said the governor can overrule the committee if it rejects the proposed vaccine rule.
Louisiana State Health Officer Joseph Kanter, MD, testified on Dec. 6 that 18 children had died of COVID-19 in Louisiana and many others had become sick because of it.
“I can’t think of another disease on that childhood schedule that we’ve lost that many kids from. In my mind, it’s very much in the public interest. But it’s the family and the parents’ decision,” Dr. Kanter said.
The addition of the vaccine is being proposed by the Louisiana Department of Health, which has added other vaccines to the required list over the years. In 2015, the legislature added meningitis as a required shot with no controversy, The Advocate said.
A version of this article first appeared on WebMD.com.
Louisiana Gov. John Bel Edwards says the state government plans to make the COVID-19 vaccine a required immunization for students 16 and older in the state’s public school system.
“I just think it’s really, really important to embrace the science and really it’s also important to not engage in misinformation,” said Gov. Edwards, a Democrat, according to The Advocate. “Absent some compelling reason, which I at present have not seen, I fully expect that we will be adding the vaccine to the schedule.”
Parents could opt out their children from the requirement with a letter from a medical provider or a simple signature in dissent, The Advocate reported. The new rule would go into effect at the start of the 2022 school year and at first would apply to students aged 16 and older.
Republican legislators voiced their opposition to the COVID-19 vaccine requirement at a hearing on Dec. 6, calling it unneeded and an example of governmental overreach.
“I believe the vaccine should be highly recommended but not mandated,” state Rep. Laurie Schlegel said, according to TV station WDSU.
State Sen. Cameron Henry of Metairie said he received “hundreds of emails” from parents asking him to prevent the rule from going into effect, WDSU said.
WDSU said the governor can overrule the committee if it rejects the proposed vaccine rule.
Louisiana State Health Officer Joseph Kanter, MD, testified on Dec. 6 that 18 children had died of COVID-19 in Louisiana and many others had become sick because of it.
“I can’t think of another disease on that childhood schedule that we’ve lost that many kids from. In my mind, it’s very much in the public interest. But it’s the family and the parents’ decision,” Dr. Kanter said.
The addition of the vaccine is being proposed by the Louisiana Department of Health, which has added other vaccines to the required list over the years. In 2015, the legislature added meningitis as a required shot with no controversy, The Advocate said.
A version of this article first appeared on WebMD.com.
Louisiana Gov. John Bel Edwards says the state government plans to make the COVID-19 vaccine a required immunization for students 16 and older in the state’s public school system.
“I just think it’s really, really important to embrace the science and really it’s also important to not engage in misinformation,” said Gov. Edwards, a Democrat, according to The Advocate. “Absent some compelling reason, which I at present have not seen, I fully expect that we will be adding the vaccine to the schedule.”
Parents could opt out their children from the requirement with a letter from a medical provider or a simple signature in dissent, The Advocate reported. The new rule would go into effect at the start of the 2022 school year and at first would apply to students aged 16 and older.
Republican legislators voiced their opposition to the COVID-19 vaccine requirement at a hearing on Dec. 6, calling it unneeded and an example of governmental overreach.
“I believe the vaccine should be highly recommended but not mandated,” state Rep. Laurie Schlegel said, according to TV station WDSU.
State Sen. Cameron Henry of Metairie said he received “hundreds of emails” from parents asking him to prevent the rule from going into effect, WDSU said.
WDSU said the governor can overrule the committee if it rejects the proposed vaccine rule.
Louisiana State Health Officer Joseph Kanter, MD, testified on Dec. 6 that 18 children had died of COVID-19 in Louisiana and many others had become sick because of it.
“I can’t think of another disease on that childhood schedule that we’ve lost that many kids from. In my mind, it’s very much in the public interest. But it’s the family and the parents’ decision,” Dr. Kanter said.
The addition of the vaccine is being proposed by the Louisiana Department of Health, which has added other vaccines to the required list over the years. In 2015, the legislature added meningitis as a required shot with no controversy, The Advocate said.
A version of this article first appeared on WebMD.com.
‘Highest survival’ with combo immunotherapy in advanced melanoma
An researchers say.
Nearly half the patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) were alive at 6½ years. Within this group, 77% had not received further systemic treatment after coming off the study drugs.
After a minimum follow-up of 77 months, median overall survival was 72.1 months in patients on the combination, which was more than three times longer than the 19.9 months with ipilimumab alone (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64) and twice as long as the 36.9 months with nivolumab alone (HR, 0.84; 95% CI, 0.67-1.04).
The results represent the longest median overall survival seen in a phase 3 trial of advanced melanoma and are evidence of “a substantial development in the melanoma treatment landscape versus the standard median survival of 8 months a decade ago,” researchers wrote in a study published online in the Journal of Clinical Oncology.
However, lead author Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, noted that the study was not designed to compare nivolumab alone with the combination. “It wasn’t powered for that. [But] what we can say is that the highest survival was in the combination group,” Dr. Wolchok told this news organization.
Dr. Wolchok cautioned that the combination therapy is not currently standard of care. “PD-1 blockade – either nivolumab or the combination – are both excellent options for care,” he added. “I can’t tell you that one of them is the standard of care because that’s too complex of a decision.”
For example, he explained, “for a patient who only has lung metastases, a single-agent PD-1 blockade might be sufficient. But if it has spread to other organs, such as the liver or bones, which are more difficult to treat, that’s when we often reach for the combination.”
Other factors that weigh into the therapeutic decision are the patient’s performance status and their so-called clinical reserve for tolerating side effects. “The likelihood of having a high-grade side effect with the combination is more than twice that of the single agent,” Dr. Wolchok said.
Until 2011, only two therapies were approved for metastatic melanoma: Chemotherapy with dacarbazine and immunotherapy with high-dose interleukin-2, neither of which was very effective at prolonging life. But patient survival changed with the advent of targeted therapies and immunotherapy. Some patients are now living for years, and as the current study shows, many have surpassed the 5-year mark and are treatment free.
The updated CheckMate 067 analysis included patients with previously untreated, unresectable stage III/IV melanoma who were randomly assigned to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (four doses) followed by nivolumab 3 mg/kg every 2 weeks (n = 314), nivolumab 3 mg/kg every 2 weeks (n = 316), or ipilimumab 3 mg/ kg every 3 weeks (four doses; n = 315).
The authors reported the 5-year overall survival rates from the trial, published in the New England Journal of Medicine in 2019 – 52% with the combination, 44% with nivolumab alone, and 26% with ipilimumab alone.
In the updated study, overall survival at 6½ years had dropped slightly to 49%, 42%, and 23%, respectively. Patients with BRAF-mutant tumors had overall survival rates of 57%, 43%, and 25% versus 46%, 42%, and 22% in those with BRAF wild-type tumors.
Overall, median investigator-assessed progression-free survival was 11.5 months with the combination, 6.9 months with nivolumab alone, and 2.9 months with ipilimumab.
The new analysis also evaluated melanoma-specific survival (MSS), which removes competing causes of deaths from the long-term follow-up. The MSS was not reached in the combination group, and was 58.7 months in the nivolumab group and 21.9 months for ipilimumab, with MSS rates at 6.5 years of 56%, 48%, and 27%, respectively.
No new safety signals were detected, but there was more immune-mediated toxicity in the combination group, the researchers reported.
“The patients will continue to be followed,” said Dr. Wolchok, “And data are still being collected.”
The trial was supported by Bristol-Myers Squibb, the National Cancer Institute, and the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre. Dr. Wolchok and coauthors reported relationships with Bristol-Myers Squibb and other drugmakers.
A version of this article first appeared on Medscape.com.
An researchers say.
Nearly half the patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) were alive at 6½ years. Within this group, 77% had not received further systemic treatment after coming off the study drugs.
After a minimum follow-up of 77 months, median overall survival was 72.1 months in patients on the combination, which was more than three times longer than the 19.9 months with ipilimumab alone (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64) and twice as long as the 36.9 months with nivolumab alone (HR, 0.84; 95% CI, 0.67-1.04).
The results represent the longest median overall survival seen in a phase 3 trial of advanced melanoma and are evidence of “a substantial development in the melanoma treatment landscape versus the standard median survival of 8 months a decade ago,” researchers wrote in a study published online in the Journal of Clinical Oncology.
However, lead author Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, noted that the study was not designed to compare nivolumab alone with the combination. “It wasn’t powered for that. [But] what we can say is that the highest survival was in the combination group,” Dr. Wolchok told this news organization.
Dr. Wolchok cautioned that the combination therapy is not currently standard of care. “PD-1 blockade – either nivolumab or the combination – are both excellent options for care,” he added. “I can’t tell you that one of them is the standard of care because that’s too complex of a decision.”
For example, he explained, “for a patient who only has lung metastases, a single-agent PD-1 blockade might be sufficient. But if it has spread to other organs, such as the liver or bones, which are more difficult to treat, that’s when we often reach for the combination.”
Other factors that weigh into the therapeutic decision are the patient’s performance status and their so-called clinical reserve for tolerating side effects. “The likelihood of having a high-grade side effect with the combination is more than twice that of the single agent,” Dr. Wolchok said.
Until 2011, only two therapies were approved for metastatic melanoma: Chemotherapy with dacarbazine and immunotherapy with high-dose interleukin-2, neither of which was very effective at prolonging life. But patient survival changed with the advent of targeted therapies and immunotherapy. Some patients are now living for years, and as the current study shows, many have surpassed the 5-year mark and are treatment free.
The updated CheckMate 067 analysis included patients with previously untreated, unresectable stage III/IV melanoma who were randomly assigned to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (four doses) followed by nivolumab 3 mg/kg every 2 weeks (n = 314), nivolumab 3 mg/kg every 2 weeks (n = 316), or ipilimumab 3 mg/ kg every 3 weeks (four doses; n = 315).
The authors reported the 5-year overall survival rates from the trial, published in the New England Journal of Medicine in 2019 – 52% with the combination, 44% with nivolumab alone, and 26% with ipilimumab alone.
In the updated study, overall survival at 6½ years had dropped slightly to 49%, 42%, and 23%, respectively. Patients with BRAF-mutant tumors had overall survival rates of 57%, 43%, and 25% versus 46%, 42%, and 22% in those with BRAF wild-type tumors.
Overall, median investigator-assessed progression-free survival was 11.5 months with the combination, 6.9 months with nivolumab alone, and 2.9 months with ipilimumab.
The new analysis also evaluated melanoma-specific survival (MSS), which removes competing causes of deaths from the long-term follow-up. The MSS was not reached in the combination group, and was 58.7 months in the nivolumab group and 21.9 months for ipilimumab, with MSS rates at 6.5 years of 56%, 48%, and 27%, respectively.
No new safety signals were detected, but there was more immune-mediated toxicity in the combination group, the researchers reported.
“The patients will continue to be followed,” said Dr. Wolchok, “And data are still being collected.”
The trial was supported by Bristol-Myers Squibb, the National Cancer Institute, and the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre. Dr. Wolchok and coauthors reported relationships with Bristol-Myers Squibb and other drugmakers.
A version of this article first appeared on Medscape.com.
An researchers say.
Nearly half the patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) were alive at 6½ years. Within this group, 77% had not received further systemic treatment after coming off the study drugs.
After a minimum follow-up of 77 months, median overall survival was 72.1 months in patients on the combination, which was more than three times longer than the 19.9 months with ipilimumab alone (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64) and twice as long as the 36.9 months with nivolumab alone (HR, 0.84; 95% CI, 0.67-1.04).
The results represent the longest median overall survival seen in a phase 3 trial of advanced melanoma and are evidence of “a substantial development in the melanoma treatment landscape versus the standard median survival of 8 months a decade ago,” researchers wrote in a study published online in the Journal of Clinical Oncology.
However, lead author Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, noted that the study was not designed to compare nivolumab alone with the combination. “It wasn’t powered for that. [But] what we can say is that the highest survival was in the combination group,” Dr. Wolchok told this news organization.
Dr. Wolchok cautioned that the combination therapy is not currently standard of care. “PD-1 blockade – either nivolumab or the combination – are both excellent options for care,” he added. “I can’t tell you that one of them is the standard of care because that’s too complex of a decision.”
For example, he explained, “for a patient who only has lung metastases, a single-agent PD-1 blockade might be sufficient. But if it has spread to other organs, such as the liver or bones, which are more difficult to treat, that’s when we often reach for the combination.”
Other factors that weigh into the therapeutic decision are the patient’s performance status and their so-called clinical reserve for tolerating side effects. “The likelihood of having a high-grade side effect with the combination is more than twice that of the single agent,” Dr. Wolchok said.
Until 2011, only two therapies were approved for metastatic melanoma: Chemotherapy with dacarbazine and immunotherapy with high-dose interleukin-2, neither of which was very effective at prolonging life. But patient survival changed with the advent of targeted therapies and immunotherapy. Some patients are now living for years, and as the current study shows, many have surpassed the 5-year mark and are treatment free.
The updated CheckMate 067 analysis included patients with previously untreated, unresectable stage III/IV melanoma who were randomly assigned to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (four doses) followed by nivolumab 3 mg/kg every 2 weeks (n = 314), nivolumab 3 mg/kg every 2 weeks (n = 316), or ipilimumab 3 mg/ kg every 3 weeks (four doses; n = 315).
The authors reported the 5-year overall survival rates from the trial, published in the New England Journal of Medicine in 2019 – 52% with the combination, 44% with nivolumab alone, and 26% with ipilimumab alone.
In the updated study, overall survival at 6½ years had dropped slightly to 49%, 42%, and 23%, respectively. Patients with BRAF-mutant tumors had overall survival rates of 57%, 43%, and 25% versus 46%, 42%, and 22% in those with BRAF wild-type tumors.
Overall, median investigator-assessed progression-free survival was 11.5 months with the combination, 6.9 months with nivolumab alone, and 2.9 months with ipilimumab.
The new analysis also evaluated melanoma-specific survival (MSS), which removes competing causes of deaths from the long-term follow-up. The MSS was not reached in the combination group, and was 58.7 months in the nivolumab group and 21.9 months for ipilimumab, with MSS rates at 6.5 years of 56%, 48%, and 27%, respectively.
No new safety signals were detected, but there was more immune-mediated toxicity in the combination group, the researchers reported.
“The patients will continue to be followed,” said Dr. Wolchok, “And data are still being collected.”
The trial was supported by Bristol-Myers Squibb, the National Cancer Institute, and the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre. Dr. Wolchok and coauthors reported relationships with Bristol-Myers Squibb and other drugmakers.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Sleep disorders and cancer: It’s complicated
Sleep apnea and other types of sleep disorders appear to elevate the risk for some types of cancer, specifically prostate cancer, more so than others. But the overall risk can be highly variable, and some sleep problems were found to be associated with a lower risk for cancer and cancer-related death, an analysis of a large observational cohort study of cardiovascular patients found.
Results of the analysis were published online in the journal Cancer Epidemiology. Investigators analyzed the presence of sleep apnea and insomnia and cancer risk in more than 8,500 patients in the Cardiovascular Health Study (CHS). “The fact that we observed certain sleep problems, like apneas, to be associated with elevated risk of some cancers but not others reflects the fact that cancer is a heterogeneous disease,” senior author Amanda Phipps, PhD, said in an interview. Dr. Phipps is an associate professor of epidemiology at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.
Variable cancer links
The researchers assessed sleep problems in two groups in the CHS: an incident cancer group of 3,930 patients and a cancer mortality group of 4,580 patients. Within those respective groups, the investigators identified 885 first-incident cancers and 804 cancer deaths with a median follow-up of 12 and 14 years. The average age of the study population was 73 years, and 57% were women.
Sleep apnea symptoms (SAS) were associated with a lower risk for incident cancers – a 16% lower baseline risk and a 24% lower time-dependent risk. The study showed no association between cancer incidence and daytime sleepiness and apneas.
However, there was a significantly elevated risk relationship between sleep problems and prostate cancer. A time-dependent analysis of apnea showed more than double the risk (hazard ratio, 2.34), and baseline snoring carried a 69% greater risk. There was also a dose-response relationship for baseline cumulative SAS, compared with not having symptoms: an HR of 1.30 for one symptom, and 2.22 for two or more symptoms.
Risks for lymphatic or hematopoietic cancers were also associated with baseline daytime sleepiness (HR, 1.81), but not with insomnia (HR, 0.54).
With regard to cancer mortality, the study found no relationship between sleep problems and cancer death. In fact, it found an overall inverse relationship with snoring (time-dependent HR, 0.73; cumulative average HR, 0.67) and baseline apnea (HR, 0.69). Likewise, patients reporting SAS had lower risks than those having no SAS: an HR of 0.90 for one symptom and 0.75 for multiple symptoms. No relationships were found between any insomnia symptom and cancer death.
“We know the pathways that lead to prostate cancer can be very different than the pathways that lead to colorectal cancer,” Dr. Phipps said. “What we don’t yet understand is why these associations differ or what mechanisms are responsible for these cancer site-specific associations.”
Need for sleep assessment
The findings don’t change much for how clinicians should evaluate cancer risks in patients with sleep problems, Dr. Phipps said. “Other studies have clearly demonstrated the implications that sleep apnea has for a variety of other important health conditions – such as cardiovascular disease – so there are already plenty of good reasons for clinicians to ask their patients about their sleep and to connect patients with resources for the diagnosis and treatment of sleep apnea,” she added. “This study provides another possible reason.”
These findings provide context for future studies of the relationship between sleep problems and cancer. “But, given that sleep is something we all do and given that sleep problems are so pervasive, it’s important that we keep trying to better understand this relationship,” Dr. Phipps said.
“My hope is that future cancer studies will build in more detailed, longitudinal information on sleep patterns to help us fill current gaps in knowledge.”
Dr. Phipps has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sleep apnea and other types of sleep disorders appear to elevate the risk for some types of cancer, specifically prostate cancer, more so than others. But the overall risk can be highly variable, and some sleep problems were found to be associated with a lower risk for cancer and cancer-related death, an analysis of a large observational cohort study of cardiovascular patients found.
Results of the analysis were published online in the journal Cancer Epidemiology. Investigators analyzed the presence of sleep apnea and insomnia and cancer risk in more than 8,500 patients in the Cardiovascular Health Study (CHS). “The fact that we observed certain sleep problems, like apneas, to be associated with elevated risk of some cancers but not others reflects the fact that cancer is a heterogeneous disease,” senior author Amanda Phipps, PhD, said in an interview. Dr. Phipps is an associate professor of epidemiology at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.
Variable cancer links
The researchers assessed sleep problems in two groups in the CHS: an incident cancer group of 3,930 patients and a cancer mortality group of 4,580 patients. Within those respective groups, the investigators identified 885 first-incident cancers and 804 cancer deaths with a median follow-up of 12 and 14 years. The average age of the study population was 73 years, and 57% were women.
Sleep apnea symptoms (SAS) were associated with a lower risk for incident cancers – a 16% lower baseline risk and a 24% lower time-dependent risk. The study showed no association between cancer incidence and daytime sleepiness and apneas.
However, there was a significantly elevated risk relationship between sleep problems and prostate cancer. A time-dependent analysis of apnea showed more than double the risk (hazard ratio, 2.34), and baseline snoring carried a 69% greater risk. There was also a dose-response relationship for baseline cumulative SAS, compared with not having symptoms: an HR of 1.30 for one symptom, and 2.22 for two or more symptoms.
Risks for lymphatic or hematopoietic cancers were also associated with baseline daytime sleepiness (HR, 1.81), but not with insomnia (HR, 0.54).
With regard to cancer mortality, the study found no relationship between sleep problems and cancer death. In fact, it found an overall inverse relationship with snoring (time-dependent HR, 0.73; cumulative average HR, 0.67) and baseline apnea (HR, 0.69). Likewise, patients reporting SAS had lower risks than those having no SAS: an HR of 0.90 for one symptom and 0.75 for multiple symptoms. No relationships were found between any insomnia symptom and cancer death.
“We know the pathways that lead to prostate cancer can be very different than the pathways that lead to colorectal cancer,” Dr. Phipps said. “What we don’t yet understand is why these associations differ or what mechanisms are responsible for these cancer site-specific associations.”
Need for sleep assessment
The findings don’t change much for how clinicians should evaluate cancer risks in patients with sleep problems, Dr. Phipps said. “Other studies have clearly demonstrated the implications that sleep apnea has for a variety of other important health conditions – such as cardiovascular disease – so there are already plenty of good reasons for clinicians to ask their patients about their sleep and to connect patients with resources for the diagnosis and treatment of sleep apnea,” she added. “This study provides another possible reason.”
These findings provide context for future studies of the relationship between sleep problems and cancer. “But, given that sleep is something we all do and given that sleep problems are so pervasive, it’s important that we keep trying to better understand this relationship,” Dr. Phipps said.
“My hope is that future cancer studies will build in more detailed, longitudinal information on sleep patterns to help us fill current gaps in knowledge.”
Dr. Phipps has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sleep apnea and other types of sleep disorders appear to elevate the risk for some types of cancer, specifically prostate cancer, more so than others. But the overall risk can be highly variable, and some sleep problems were found to be associated with a lower risk for cancer and cancer-related death, an analysis of a large observational cohort study of cardiovascular patients found.
Results of the analysis were published online in the journal Cancer Epidemiology. Investigators analyzed the presence of sleep apnea and insomnia and cancer risk in more than 8,500 patients in the Cardiovascular Health Study (CHS). “The fact that we observed certain sleep problems, like apneas, to be associated with elevated risk of some cancers but not others reflects the fact that cancer is a heterogeneous disease,” senior author Amanda Phipps, PhD, said in an interview. Dr. Phipps is an associate professor of epidemiology at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.
Variable cancer links
The researchers assessed sleep problems in two groups in the CHS: an incident cancer group of 3,930 patients and a cancer mortality group of 4,580 patients. Within those respective groups, the investigators identified 885 first-incident cancers and 804 cancer deaths with a median follow-up of 12 and 14 years. The average age of the study population was 73 years, and 57% were women.
Sleep apnea symptoms (SAS) were associated with a lower risk for incident cancers – a 16% lower baseline risk and a 24% lower time-dependent risk. The study showed no association between cancer incidence and daytime sleepiness and apneas.
However, there was a significantly elevated risk relationship between sleep problems and prostate cancer. A time-dependent analysis of apnea showed more than double the risk (hazard ratio, 2.34), and baseline snoring carried a 69% greater risk. There was also a dose-response relationship for baseline cumulative SAS, compared with not having symptoms: an HR of 1.30 for one symptom, and 2.22 for two or more symptoms.
Risks for lymphatic or hematopoietic cancers were also associated with baseline daytime sleepiness (HR, 1.81), but not with insomnia (HR, 0.54).
With regard to cancer mortality, the study found no relationship between sleep problems and cancer death. In fact, it found an overall inverse relationship with snoring (time-dependent HR, 0.73; cumulative average HR, 0.67) and baseline apnea (HR, 0.69). Likewise, patients reporting SAS had lower risks than those having no SAS: an HR of 0.90 for one symptom and 0.75 for multiple symptoms. No relationships were found between any insomnia symptom and cancer death.
“We know the pathways that lead to prostate cancer can be very different than the pathways that lead to colorectal cancer,” Dr. Phipps said. “What we don’t yet understand is why these associations differ or what mechanisms are responsible for these cancer site-specific associations.”
Need for sleep assessment
The findings don’t change much for how clinicians should evaluate cancer risks in patients with sleep problems, Dr. Phipps said. “Other studies have clearly demonstrated the implications that sleep apnea has for a variety of other important health conditions – such as cardiovascular disease – so there are already plenty of good reasons for clinicians to ask their patients about their sleep and to connect patients with resources for the diagnosis and treatment of sleep apnea,” she added. “This study provides another possible reason.”
These findings provide context for future studies of the relationship between sleep problems and cancer. “But, given that sleep is something we all do and given that sleep problems are so pervasive, it’s important that we keep trying to better understand this relationship,” Dr. Phipps said.
“My hope is that future cancer studies will build in more detailed, longitudinal information on sleep patterns to help us fill current gaps in knowledge.”
Dr. Phipps has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CANCER EPIDEMIOLOGY
Large analysis confirms safety of nipple-sparing mastectomy
A new analysis of over 22,000 mastectomy patients confirms what smaller studies have indicated: Patients who undergo nipple-sparing mastectomy have overall and disease-free survival similar to that of those who receive a total mastectomy.
When nipple-sparing mastectomy was introduced, many experts felt uneasy about opting for the less invasive procedure, recalled Rosa Hwang, MD, associate medical director for breast surgery at MD Anderson Cancer Center in Houston. “The concern was leaving all this skin,” said Dr. Hwang. “Are you going to leave cancer behind” and increase the risk of local recurrence?
Over the past 2 decades, the number of patients undergoing nipple-sparing mastectomy increased and, in turn, studies began to demonstrate the safety of the procedure.
However, large analyses evaluating long-term outcomes – namely, overall survival and breast cancer-specific survival – of nipple-sparing mastectomy were still lacking.
The latest study, published online Nov. 20 in Annals of Surgical Oncology, compared the long-term prognosis and survival benefits of nipple-sparing to total mastectomy in thousands of women. The analysis, which pulled data from the SEER cancer database, included 5,765 patients who underwent the nipple-sparing procedure and 17,289 patients who had a total mastectomy.
The authors found that overall survival and breast cancer–specific survival were similar for women undergoing nipple-sparing mastectomy and those receiving a total mastectomy. In fact, over the long-term, the nipple-sparing group slightly edged out the total mastectomy group in overall survival (94.61% vs. 93% at 5 years and 86.34% vs. 83.48% at 10 years, respectively) and in breast cancer-specific survival rates (96.16% vs. 95.74% at 5 years, and 92.2% vs. 91.37% at 10 years). The differences, however, were not significant.
The study also found that certain subgroups – including White women, women over age 46, those with a median household income of $70,000 or more, hormone receptor-positive, and HER2 negative – had significantly better overall survival rate with the nipple-sparing procedure (P < .05). However, the authors noted, the survival advantage in the nipple-sparing group did not extend to breast cancer–specific survival.
Dr. Hwang, who was not involved in the current analysis, said the significant overall survival result in the subgroup analysis was surprising because “there’s no biological reason why one would expect that to be true.”
Given that the subgroups did not demonstrate better breast cancer–specific survival, Dr. Hwang believes the overall survival finding may have more to do with comorbidities, which the study did not account for, than type of mastectomy.
When choosing who is eligible for a nipple-sparing mastectomy, “We’re more selective,” Dr. Hwang said. For instance, patients with uncontrolled diabetes or who smoke are unlikely to be candidates. “So, I think it’s possible that medical comorbidities and medical conditions between these groups [were] different.”
According to the authors, coding inconsistencies represent another possible weakness of the study. From 1998 to 2010, “the term ‘nipple-sparing mastectomy’ was coded as a [total mastectomy] with the ‘subcutaneous mastectomy’ code.” It’s possible that some patients receiving the nipple-sparing procedure before 2011 were not appropriately coded in the current study.
Moving forward, a large prospective study that includes comorbidities would be helpful, but overall the study helps validate that “nipple-sparing mastectomy is a safe operation for selected patients,” Dr. Hwang said.
A version of this article first appeared on Medscape.com.
A new analysis of over 22,000 mastectomy patients confirms what smaller studies have indicated: Patients who undergo nipple-sparing mastectomy have overall and disease-free survival similar to that of those who receive a total mastectomy.
When nipple-sparing mastectomy was introduced, many experts felt uneasy about opting for the less invasive procedure, recalled Rosa Hwang, MD, associate medical director for breast surgery at MD Anderson Cancer Center in Houston. “The concern was leaving all this skin,” said Dr. Hwang. “Are you going to leave cancer behind” and increase the risk of local recurrence?
Over the past 2 decades, the number of patients undergoing nipple-sparing mastectomy increased and, in turn, studies began to demonstrate the safety of the procedure.
However, large analyses evaluating long-term outcomes – namely, overall survival and breast cancer-specific survival – of nipple-sparing mastectomy were still lacking.
The latest study, published online Nov. 20 in Annals of Surgical Oncology, compared the long-term prognosis and survival benefits of nipple-sparing to total mastectomy in thousands of women. The analysis, which pulled data from the SEER cancer database, included 5,765 patients who underwent the nipple-sparing procedure and 17,289 patients who had a total mastectomy.
The authors found that overall survival and breast cancer–specific survival were similar for women undergoing nipple-sparing mastectomy and those receiving a total mastectomy. In fact, over the long-term, the nipple-sparing group slightly edged out the total mastectomy group in overall survival (94.61% vs. 93% at 5 years and 86.34% vs. 83.48% at 10 years, respectively) and in breast cancer-specific survival rates (96.16% vs. 95.74% at 5 years, and 92.2% vs. 91.37% at 10 years). The differences, however, were not significant.
The study also found that certain subgroups – including White women, women over age 46, those with a median household income of $70,000 or more, hormone receptor-positive, and HER2 negative – had significantly better overall survival rate with the nipple-sparing procedure (P < .05). However, the authors noted, the survival advantage in the nipple-sparing group did not extend to breast cancer–specific survival.
Dr. Hwang, who was not involved in the current analysis, said the significant overall survival result in the subgroup analysis was surprising because “there’s no biological reason why one would expect that to be true.”
Given that the subgroups did not demonstrate better breast cancer–specific survival, Dr. Hwang believes the overall survival finding may have more to do with comorbidities, which the study did not account for, than type of mastectomy.
When choosing who is eligible for a nipple-sparing mastectomy, “We’re more selective,” Dr. Hwang said. For instance, patients with uncontrolled diabetes or who smoke are unlikely to be candidates. “So, I think it’s possible that medical comorbidities and medical conditions between these groups [were] different.”
According to the authors, coding inconsistencies represent another possible weakness of the study. From 1998 to 2010, “the term ‘nipple-sparing mastectomy’ was coded as a [total mastectomy] with the ‘subcutaneous mastectomy’ code.” It’s possible that some patients receiving the nipple-sparing procedure before 2011 were not appropriately coded in the current study.
Moving forward, a large prospective study that includes comorbidities would be helpful, but overall the study helps validate that “nipple-sparing mastectomy is a safe operation for selected patients,” Dr. Hwang said.
A version of this article first appeared on Medscape.com.
A new analysis of over 22,000 mastectomy patients confirms what smaller studies have indicated: Patients who undergo nipple-sparing mastectomy have overall and disease-free survival similar to that of those who receive a total mastectomy.
When nipple-sparing mastectomy was introduced, many experts felt uneasy about opting for the less invasive procedure, recalled Rosa Hwang, MD, associate medical director for breast surgery at MD Anderson Cancer Center in Houston. “The concern was leaving all this skin,” said Dr. Hwang. “Are you going to leave cancer behind” and increase the risk of local recurrence?
Over the past 2 decades, the number of patients undergoing nipple-sparing mastectomy increased and, in turn, studies began to demonstrate the safety of the procedure.
However, large analyses evaluating long-term outcomes – namely, overall survival and breast cancer-specific survival – of nipple-sparing mastectomy were still lacking.
The latest study, published online Nov. 20 in Annals of Surgical Oncology, compared the long-term prognosis and survival benefits of nipple-sparing to total mastectomy in thousands of women. The analysis, which pulled data from the SEER cancer database, included 5,765 patients who underwent the nipple-sparing procedure and 17,289 patients who had a total mastectomy.
The authors found that overall survival and breast cancer–specific survival were similar for women undergoing nipple-sparing mastectomy and those receiving a total mastectomy. In fact, over the long-term, the nipple-sparing group slightly edged out the total mastectomy group in overall survival (94.61% vs. 93% at 5 years and 86.34% vs. 83.48% at 10 years, respectively) and in breast cancer-specific survival rates (96.16% vs. 95.74% at 5 years, and 92.2% vs. 91.37% at 10 years). The differences, however, were not significant.
The study also found that certain subgroups – including White women, women over age 46, those with a median household income of $70,000 or more, hormone receptor-positive, and HER2 negative – had significantly better overall survival rate with the nipple-sparing procedure (P < .05). However, the authors noted, the survival advantage in the nipple-sparing group did not extend to breast cancer–specific survival.
Dr. Hwang, who was not involved in the current analysis, said the significant overall survival result in the subgroup analysis was surprising because “there’s no biological reason why one would expect that to be true.”
Given that the subgroups did not demonstrate better breast cancer–specific survival, Dr. Hwang believes the overall survival finding may have more to do with comorbidities, which the study did not account for, than type of mastectomy.
When choosing who is eligible for a nipple-sparing mastectomy, “We’re more selective,” Dr. Hwang said. For instance, patients with uncontrolled diabetes or who smoke are unlikely to be candidates. “So, I think it’s possible that medical comorbidities and medical conditions between these groups [were] different.”
According to the authors, coding inconsistencies represent another possible weakness of the study. From 1998 to 2010, “the term ‘nipple-sparing mastectomy’ was coded as a [total mastectomy] with the ‘subcutaneous mastectomy’ code.” It’s possible that some patients receiving the nipple-sparing procedure before 2011 were not appropriately coded in the current study.
Moving forward, a large prospective study that includes comorbidities would be helpful, but overall the study helps validate that “nipple-sparing mastectomy is a safe operation for selected patients,” Dr. Hwang said.
A version of this article first appeared on Medscape.com.
Can aspirin prolong survival in patients with NSCLC?
(NSCLC), according to a new study from Taiwan.
The analysis, published online Nov. 22 in BMC Cancer , adds another data point to a small and inconsistent evidence base.
“Despite the need for future prospective randomized clinical trials, aspirin may be considered as an additional treatment for inoperable NSCLC patients,” Ming-Szu Hung, MD, of Chang-Gung University, Taoyuan City, and colleagues write.
The current literature suggests that the over-the-counter medication may help ward off various types of cancer, including lung cancer, but the various study findings do not always align. For lung-cancer survival, in particular, a few observational studies have found increased survival among aspirin users while others have not.
To help bring clarity to the literature, Dr. Hung’s team examined data from Taiwan’s National Health Insurance Research Database on more than 38,000 patients diagnosed with NSCLC between 2000 and 2012, almost 5,000 of whom were taking aspirin at the time of diagnosis.
The researchers found that aspirin users survived for a median of 1.73 years, compared with 1.30 years for nonusers. Taking the drug was associated with longer overall survival in time-varying covariate analysis (hazard ratio, 0.83; 95% CI, 0.80-0.86). This finding was confirmed in a propensity-score analysis of 4,932 matched pairs (HR, 0.79; 95% CI, 0.75-0.83).
“These results warrant further randomized clinical trials to evaluate the actual role of aspirin in the treatment of NSCLC patients,” the researchers conclude.
But Úna McMenamin, PhD, a cancer epidemiologist at Queen’s University Belfast, Ireland, was not convinced by the study’s methods.
While she praised its large size and use of population-based health registers, she expressed concern about the potential for reverse causation, “as it is unclear whether authors lagged the aspirin exposure in the cohort of lung cancer patients.”
There is evidence that common medications such as aspirin may be withdrawn from patients who are thought to be near the end of their life, Dr. McMenamin told this news organization. When not factored into the statistical analysis, aspirin may appear “to be spuriously associated with a reduced risk of death when, in fact, no association may be present.”
Previous studies of aspirin use in lung cancer patients that have included a lag, such as one Dr. McMenamin and colleagues conducted in 2015, have found no evidence of a protective effect.
That is why, according to Dr. McMenamin, “additional population-based studies, in diverse populations, are required to investigate the association between aspirin use and survival outcomes in lung-cancer patients to determine whether randomized controlled trials are warranted in this patient group.”
In addition, she noted, “any potential benefit of aspirin in lung cancer patients needs to be balanced against known adverse events associated with prolonged aspirin use, such as gastrointestinal bleeding.”
Dr. Hung did not reply to requests for comment.
The study had no funding, and the researchers report no conflicts of interest.
A version of this article first appeared on Medscape.com.
(NSCLC), according to a new study from Taiwan.
The analysis, published online Nov. 22 in BMC Cancer , adds another data point to a small and inconsistent evidence base.
“Despite the need for future prospective randomized clinical trials, aspirin may be considered as an additional treatment for inoperable NSCLC patients,” Ming-Szu Hung, MD, of Chang-Gung University, Taoyuan City, and colleagues write.
The current literature suggests that the over-the-counter medication may help ward off various types of cancer, including lung cancer, but the various study findings do not always align. For lung-cancer survival, in particular, a few observational studies have found increased survival among aspirin users while others have not.
To help bring clarity to the literature, Dr. Hung’s team examined data from Taiwan’s National Health Insurance Research Database on more than 38,000 patients diagnosed with NSCLC between 2000 and 2012, almost 5,000 of whom were taking aspirin at the time of diagnosis.
The researchers found that aspirin users survived for a median of 1.73 years, compared with 1.30 years for nonusers. Taking the drug was associated with longer overall survival in time-varying covariate analysis (hazard ratio, 0.83; 95% CI, 0.80-0.86). This finding was confirmed in a propensity-score analysis of 4,932 matched pairs (HR, 0.79; 95% CI, 0.75-0.83).
“These results warrant further randomized clinical trials to evaluate the actual role of aspirin in the treatment of NSCLC patients,” the researchers conclude.
But Úna McMenamin, PhD, a cancer epidemiologist at Queen’s University Belfast, Ireland, was not convinced by the study’s methods.
While she praised its large size and use of population-based health registers, she expressed concern about the potential for reverse causation, “as it is unclear whether authors lagged the aspirin exposure in the cohort of lung cancer patients.”
There is evidence that common medications such as aspirin may be withdrawn from patients who are thought to be near the end of their life, Dr. McMenamin told this news organization. When not factored into the statistical analysis, aspirin may appear “to be spuriously associated with a reduced risk of death when, in fact, no association may be present.”
Previous studies of aspirin use in lung cancer patients that have included a lag, such as one Dr. McMenamin and colleagues conducted in 2015, have found no evidence of a protective effect.
That is why, according to Dr. McMenamin, “additional population-based studies, in diverse populations, are required to investigate the association between aspirin use and survival outcomes in lung-cancer patients to determine whether randomized controlled trials are warranted in this patient group.”
In addition, she noted, “any potential benefit of aspirin in lung cancer patients needs to be balanced against known adverse events associated with prolonged aspirin use, such as gastrointestinal bleeding.”
Dr. Hung did not reply to requests for comment.
The study had no funding, and the researchers report no conflicts of interest.
A version of this article first appeared on Medscape.com.
(NSCLC), according to a new study from Taiwan.
The analysis, published online Nov. 22 in BMC Cancer , adds another data point to a small and inconsistent evidence base.
“Despite the need for future prospective randomized clinical trials, aspirin may be considered as an additional treatment for inoperable NSCLC patients,” Ming-Szu Hung, MD, of Chang-Gung University, Taoyuan City, and colleagues write.
The current literature suggests that the over-the-counter medication may help ward off various types of cancer, including lung cancer, but the various study findings do not always align. For lung-cancer survival, in particular, a few observational studies have found increased survival among aspirin users while others have not.
To help bring clarity to the literature, Dr. Hung’s team examined data from Taiwan’s National Health Insurance Research Database on more than 38,000 patients diagnosed with NSCLC between 2000 and 2012, almost 5,000 of whom were taking aspirin at the time of diagnosis.
The researchers found that aspirin users survived for a median of 1.73 years, compared with 1.30 years for nonusers. Taking the drug was associated with longer overall survival in time-varying covariate analysis (hazard ratio, 0.83; 95% CI, 0.80-0.86). This finding was confirmed in a propensity-score analysis of 4,932 matched pairs (HR, 0.79; 95% CI, 0.75-0.83).
“These results warrant further randomized clinical trials to evaluate the actual role of aspirin in the treatment of NSCLC patients,” the researchers conclude.
But Úna McMenamin, PhD, a cancer epidemiologist at Queen’s University Belfast, Ireland, was not convinced by the study’s methods.
While she praised its large size and use of population-based health registers, she expressed concern about the potential for reverse causation, “as it is unclear whether authors lagged the aspirin exposure in the cohort of lung cancer patients.”
There is evidence that common medications such as aspirin may be withdrawn from patients who are thought to be near the end of their life, Dr. McMenamin told this news organization. When not factored into the statistical analysis, aspirin may appear “to be spuriously associated with a reduced risk of death when, in fact, no association may be present.”
Previous studies of aspirin use in lung cancer patients that have included a lag, such as one Dr. McMenamin and colleagues conducted in 2015, have found no evidence of a protective effect.
That is why, according to Dr. McMenamin, “additional population-based studies, in diverse populations, are required to investigate the association between aspirin use and survival outcomes in lung-cancer patients to determine whether randomized controlled trials are warranted in this patient group.”
In addition, she noted, “any potential benefit of aspirin in lung cancer patients needs to be balanced against known adverse events associated with prolonged aspirin use, such as gastrointestinal bleeding.”
Dr. Hung did not reply to requests for comment.
The study had no funding, and the researchers report no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM BMC CANCER
What’s hot at the world’s premiere breast cancer meeting
Dr. Arteaga, the meeting’s codirector, said the first-ever hybrid symposium will take place virtually from Dec. 7 to 10 as well as in person. Online availability appears to be a boon to attendance, with a record 9,325 registrants for the 2020 symposium, held only virtually because of the COVID-19 pandemic.
The meeting will have an app available, which can be accessed by searching “San Antonio Breast Cancer Symposium” (Google Play for Android, Apple for iOS) and downloading, or by going to www.core-apps.com/dl/sabcs from a desktop computer.
Dr. Arteaga provided a sneak peek of the most exciting research being presented at the upcoming meeting.
On the horizon for advanced breast cancer
A “very important” study of an investigational oral agent employed in heavily pretreated postmenopausal women with estrogen receptor–positive (ER+) advanced breast cancer headlines the meeting.
This international, multicenter trial could have “practice-changing implications,” Dr. Arteaga said in an interview.
The phase 3 EMERALD trial (abstract GS2-02) pits elacestrant, a selective estrogen receptor degrader (SERD), against standard endocrine therapy (fulvestrant or an aromatase inhibitor) in patients with metastatic breast cancer whose disease has progressed after treatment with at least one endocrine therapy and a CDK4/6 inhibitor.
The trial is important because many patients with breast cancer have estrogen receptor mutations, which are a “major mechanism of [drug] resistance” and thus progression on earlier therapy, Dr. Arteaga said.
Elacestrant is in good company among a plethora of oral SERDs under investigation in advanced breast cancer; however, currently, fulvestrant – which requires an intramuscular injection in the buttocks every month – is the only approved SERD.
“There’s plenty of preclinical data that suggest that these drugs [SERDs] may have activity against these mutant forms of the receptor, which occur in up to 40% of patients with advanced ER+ breast cancer,” he explained.
Researchers will present data on two primary outcome measures from the phase 3 trial: progression-free survival (PFS) based on mutations of the estrogen receptor 1 gene (ESR1-mut) and PFS in all subjects regardless of ESR1 status.
In addition to the EMERALD trial, PADA-1 (abstract GS3-05) is another important randomized, phase 3 trial focused on treating estrogen receptor mutations in patients with metastatic disease, said Dr. Arteaga.
The trial has enrolled patients with ER+ metastatic breast cancer who received an aromatase inhibitor (letrozole, anastrozole, or exemestane) and the CDK4/6 inhibitor palbociclib as first-line therapy.
In step 1 of the trial, approximately 1,000 patients were screened for circulating blood ESR1 mutation detection at regular intervals while being treated with palbociclib and an aromatase inhibitor in a continuous scheme until tumor progression or ESR1 mutation detection.
In step 2, up to 200 patients with a rising circulating ESR1 mutation and no tumor progression were randomized 1:1 to no change in therapy until tumor progression or to receive palbociclib plus fulvestrant until tumor progression.
The trial examines the safety and efficacy of “a clinical conundrum that we face” in this setting: whether or not to switch treatment from an aromatase inhibitor to fulvestrant while continuing a CDK4/6 inhibitor at the sign of mutation detection, Dr. Arteaga explained.
Refining who gets the ‘kitchen sink’
Dr. Arteaga highlighted two trials focused on the immune checkpoint inhibitor pembrolizumab.
The phase 3 KEYNOTE-522 study led to the approval of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer (TNBC) in July 2021. At this year’s SABCS, researchers will present new data from KEYNOTE-522 (abstract GS1-01), representing final results from the trial’s event-free survival (EFS) outcome.
Previously, investigators reported a statistically significant and clinically meaningful improvement in EFS. These data suggest “that deploying immunotherapy early before surgery ... may be curative in some patients,” Dr. Arteaga said. The new data will allow the “robustness and consistency” of the earlier findings to be assessed.
But, he added, this is a “tough” treatment, which includes five drugs. “It’s the kitchen sink, and not everybody needs the kitchen sink. It’s important to refine these findings. Some patients may not need pembrolizumab, but some do.”
The second trial exploring pembrolizumab – KEYNOTE-355 (abstract GS1-02) – mirrors KEYNOTE-522 but in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1.
Previously, investigators reported that pembrolizumab combined with chemotherapy showed statistically significant improvements in overall survival and PFS compared to placebo plus chemotherapy. At the 2021 SABCS, researchers will provide final study results, including outcomes in subgroups of patients by additional combined positive score cutoffs.
Metformin trial: ‘This is it’
Dr. Arteaga highlighted CCTGMA.32 (abstract GS1-08), a phase 3 randomized, placebo-controlled adjuvant trial of the diabetes drug metformin versus placebo in early breast cancer. Results of the primary efficacy analysis of the trial will be presented at the meeting.
The Canadian-led study seeks to determine if metformin can decrease breast cancer cell growth and work with cancer therapies to prevent disease recurrence. The study design calls for patients to take twice-daily oral metformin or placebo pills for up to 5 years in the absence of disease progression.
The primary outcome of the 3,500-plus patient trial is invasive disease-free survival in hormone receptor (ER and PgR) negative and positive (ER and/or PgR) subgroups.
“Metformin has actually been associated with improved survival [in breast cancer] in patients on chemotherapy. But we don’t know exactly how,” he said. “There’s never been a head-to-head comparison in the adjuvant setting [before]. This is it.”
TKI for breast cancer with brain mets
The SABCS codirector spotlighted an updated overall survival analysis of the randomized phase 3 PHOEBE trial (abstract GS3-02).
Previous research confirmed the superiority of pyrotinib, a novel TKI targeting HER1, HER2, and HER4, over lapatinib when given in combination with capecitabine in HER2-positive metastatic breast cancer.
In the United States, the lapatinib-capecitabine combination is “mostly used” in patients with HER2 metastatic disease and brain metastases who also undergo stereotactic radiation, Dr. Arteaga said.
This use has continued despite groundbreaking results from the HER2CLIMB trial, featuring the TKI tucatinib, he said.
As reported last year, adding tucatinib to trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases increased median overall survival from 12 months to 18.1 months. The results were called the first of their kind at that time.
The pyrotinib study may matter to American clinicians because pyrotinib is used mostly in China, not the United States, and this analysis suggests that pyrotinib could be part of the armamentarium in the United States, alongside tucatinib.
TKIs are like Coke and Pepsi, Dr. Arteaga said: “Similar but not identical.” Therefore, it is worth taking a look at the new study, he said. “There may be some benefit in having more than one [TKI] in the therapeutic armamentarium.”
Dr. Arteaga receives or has received grant support from Pfizer and Lilly and serves or has served in a scientific advisory role with Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, and the Susan G. Komen Foundation. He also holds minor stock options from Provista.
A version of this article first appeared on Medscape.com.
Dr. Arteaga, the meeting’s codirector, said the first-ever hybrid symposium will take place virtually from Dec. 7 to 10 as well as in person. Online availability appears to be a boon to attendance, with a record 9,325 registrants for the 2020 symposium, held only virtually because of the COVID-19 pandemic.
The meeting will have an app available, which can be accessed by searching “San Antonio Breast Cancer Symposium” (Google Play for Android, Apple for iOS) and downloading, or by going to www.core-apps.com/dl/sabcs from a desktop computer.
Dr. Arteaga provided a sneak peek of the most exciting research being presented at the upcoming meeting.
On the horizon for advanced breast cancer
A “very important” study of an investigational oral agent employed in heavily pretreated postmenopausal women with estrogen receptor–positive (ER+) advanced breast cancer headlines the meeting.
This international, multicenter trial could have “practice-changing implications,” Dr. Arteaga said in an interview.
The phase 3 EMERALD trial (abstract GS2-02) pits elacestrant, a selective estrogen receptor degrader (SERD), against standard endocrine therapy (fulvestrant or an aromatase inhibitor) in patients with metastatic breast cancer whose disease has progressed after treatment with at least one endocrine therapy and a CDK4/6 inhibitor.
The trial is important because many patients with breast cancer have estrogen receptor mutations, which are a “major mechanism of [drug] resistance” and thus progression on earlier therapy, Dr. Arteaga said.
Elacestrant is in good company among a plethora of oral SERDs under investigation in advanced breast cancer; however, currently, fulvestrant – which requires an intramuscular injection in the buttocks every month – is the only approved SERD.
“There’s plenty of preclinical data that suggest that these drugs [SERDs] may have activity against these mutant forms of the receptor, which occur in up to 40% of patients with advanced ER+ breast cancer,” he explained.
Researchers will present data on two primary outcome measures from the phase 3 trial: progression-free survival (PFS) based on mutations of the estrogen receptor 1 gene (ESR1-mut) and PFS in all subjects regardless of ESR1 status.
In addition to the EMERALD trial, PADA-1 (abstract GS3-05) is another important randomized, phase 3 trial focused on treating estrogen receptor mutations in patients with metastatic disease, said Dr. Arteaga.
The trial has enrolled patients with ER+ metastatic breast cancer who received an aromatase inhibitor (letrozole, anastrozole, or exemestane) and the CDK4/6 inhibitor palbociclib as first-line therapy.
In step 1 of the trial, approximately 1,000 patients were screened for circulating blood ESR1 mutation detection at regular intervals while being treated with palbociclib and an aromatase inhibitor in a continuous scheme until tumor progression or ESR1 mutation detection.
In step 2, up to 200 patients with a rising circulating ESR1 mutation and no tumor progression were randomized 1:1 to no change in therapy until tumor progression or to receive palbociclib plus fulvestrant until tumor progression.
The trial examines the safety and efficacy of “a clinical conundrum that we face” in this setting: whether or not to switch treatment from an aromatase inhibitor to fulvestrant while continuing a CDK4/6 inhibitor at the sign of mutation detection, Dr. Arteaga explained.
Refining who gets the ‘kitchen sink’
Dr. Arteaga highlighted two trials focused on the immune checkpoint inhibitor pembrolizumab.
The phase 3 KEYNOTE-522 study led to the approval of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer (TNBC) in July 2021. At this year’s SABCS, researchers will present new data from KEYNOTE-522 (abstract GS1-01), representing final results from the trial’s event-free survival (EFS) outcome.
Previously, investigators reported a statistically significant and clinically meaningful improvement in EFS. These data suggest “that deploying immunotherapy early before surgery ... may be curative in some patients,” Dr. Arteaga said. The new data will allow the “robustness and consistency” of the earlier findings to be assessed.
But, he added, this is a “tough” treatment, which includes five drugs. “It’s the kitchen sink, and not everybody needs the kitchen sink. It’s important to refine these findings. Some patients may not need pembrolizumab, but some do.”
The second trial exploring pembrolizumab – KEYNOTE-355 (abstract GS1-02) – mirrors KEYNOTE-522 but in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1.
Previously, investigators reported that pembrolizumab combined with chemotherapy showed statistically significant improvements in overall survival and PFS compared to placebo plus chemotherapy. At the 2021 SABCS, researchers will provide final study results, including outcomes in subgroups of patients by additional combined positive score cutoffs.
Metformin trial: ‘This is it’
Dr. Arteaga highlighted CCTGMA.32 (abstract GS1-08), a phase 3 randomized, placebo-controlled adjuvant trial of the diabetes drug metformin versus placebo in early breast cancer. Results of the primary efficacy analysis of the trial will be presented at the meeting.
The Canadian-led study seeks to determine if metformin can decrease breast cancer cell growth and work with cancer therapies to prevent disease recurrence. The study design calls for patients to take twice-daily oral metformin or placebo pills for up to 5 years in the absence of disease progression.
The primary outcome of the 3,500-plus patient trial is invasive disease-free survival in hormone receptor (ER and PgR) negative and positive (ER and/or PgR) subgroups.
“Metformin has actually been associated with improved survival [in breast cancer] in patients on chemotherapy. But we don’t know exactly how,” he said. “There’s never been a head-to-head comparison in the adjuvant setting [before]. This is it.”
TKI for breast cancer with brain mets
The SABCS codirector spotlighted an updated overall survival analysis of the randomized phase 3 PHOEBE trial (abstract GS3-02).
Previous research confirmed the superiority of pyrotinib, a novel TKI targeting HER1, HER2, and HER4, over lapatinib when given in combination with capecitabine in HER2-positive metastatic breast cancer.
In the United States, the lapatinib-capecitabine combination is “mostly used” in patients with HER2 metastatic disease and brain metastases who also undergo stereotactic radiation, Dr. Arteaga said.
This use has continued despite groundbreaking results from the HER2CLIMB trial, featuring the TKI tucatinib, he said.
As reported last year, adding tucatinib to trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases increased median overall survival from 12 months to 18.1 months. The results were called the first of their kind at that time.
The pyrotinib study may matter to American clinicians because pyrotinib is used mostly in China, not the United States, and this analysis suggests that pyrotinib could be part of the armamentarium in the United States, alongside tucatinib.
TKIs are like Coke and Pepsi, Dr. Arteaga said: “Similar but not identical.” Therefore, it is worth taking a look at the new study, he said. “There may be some benefit in having more than one [TKI] in the therapeutic armamentarium.”
Dr. Arteaga receives or has received grant support from Pfizer and Lilly and serves or has served in a scientific advisory role with Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, and the Susan G. Komen Foundation. He also holds minor stock options from Provista.
A version of this article first appeared on Medscape.com.
Dr. Arteaga, the meeting’s codirector, said the first-ever hybrid symposium will take place virtually from Dec. 7 to 10 as well as in person. Online availability appears to be a boon to attendance, with a record 9,325 registrants for the 2020 symposium, held only virtually because of the COVID-19 pandemic.
The meeting will have an app available, which can be accessed by searching “San Antonio Breast Cancer Symposium” (Google Play for Android, Apple for iOS) and downloading, or by going to www.core-apps.com/dl/sabcs from a desktop computer.
Dr. Arteaga provided a sneak peek of the most exciting research being presented at the upcoming meeting.
On the horizon for advanced breast cancer
A “very important” study of an investigational oral agent employed in heavily pretreated postmenopausal women with estrogen receptor–positive (ER+) advanced breast cancer headlines the meeting.
This international, multicenter trial could have “practice-changing implications,” Dr. Arteaga said in an interview.
The phase 3 EMERALD trial (abstract GS2-02) pits elacestrant, a selective estrogen receptor degrader (SERD), against standard endocrine therapy (fulvestrant or an aromatase inhibitor) in patients with metastatic breast cancer whose disease has progressed after treatment with at least one endocrine therapy and a CDK4/6 inhibitor.
The trial is important because many patients with breast cancer have estrogen receptor mutations, which are a “major mechanism of [drug] resistance” and thus progression on earlier therapy, Dr. Arteaga said.
Elacestrant is in good company among a plethora of oral SERDs under investigation in advanced breast cancer; however, currently, fulvestrant – which requires an intramuscular injection in the buttocks every month – is the only approved SERD.
“There’s plenty of preclinical data that suggest that these drugs [SERDs] may have activity against these mutant forms of the receptor, which occur in up to 40% of patients with advanced ER+ breast cancer,” he explained.
Researchers will present data on two primary outcome measures from the phase 3 trial: progression-free survival (PFS) based on mutations of the estrogen receptor 1 gene (ESR1-mut) and PFS in all subjects regardless of ESR1 status.
In addition to the EMERALD trial, PADA-1 (abstract GS3-05) is another important randomized, phase 3 trial focused on treating estrogen receptor mutations in patients with metastatic disease, said Dr. Arteaga.
The trial has enrolled patients with ER+ metastatic breast cancer who received an aromatase inhibitor (letrozole, anastrozole, or exemestane) and the CDK4/6 inhibitor palbociclib as first-line therapy.
In step 1 of the trial, approximately 1,000 patients were screened for circulating blood ESR1 mutation detection at regular intervals while being treated with palbociclib and an aromatase inhibitor in a continuous scheme until tumor progression or ESR1 mutation detection.
In step 2, up to 200 patients with a rising circulating ESR1 mutation and no tumor progression were randomized 1:1 to no change in therapy until tumor progression or to receive palbociclib plus fulvestrant until tumor progression.
The trial examines the safety and efficacy of “a clinical conundrum that we face” in this setting: whether or not to switch treatment from an aromatase inhibitor to fulvestrant while continuing a CDK4/6 inhibitor at the sign of mutation detection, Dr. Arteaga explained.
Refining who gets the ‘kitchen sink’
Dr. Arteaga highlighted two trials focused on the immune checkpoint inhibitor pembrolizumab.
The phase 3 KEYNOTE-522 study led to the approval of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer (TNBC) in July 2021. At this year’s SABCS, researchers will present new data from KEYNOTE-522 (abstract GS1-01), representing final results from the trial’s event-free survival (EFS) outcome.
Previously, investigators reported a statistically significant and clinically meaningful improvement in EFS. These data suggest “that deploying immunotherapy early before surgery ... may be curative in some patients,” Dr. Arteaga said. The new data will allow the “robustness and consistency” of the earlier findings to be assessed.
But, he added, this is a “tough” treatment, which includes five drugs. “It’s the kitchen sink, and not everybody needs the kitchen sink. It’s important to refine these findings. Some patients may not need pembrolizumab, but some do.”
The second trial exploring pembrolizumab – KEYNOTE-355 (abstract GS1-02) – mirrors KEYNOTE-522 but in patients with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1.
Previously, investigators reported that pembrolizumab combined with chemotherapy showed statistically significant improvements in overall survival and PFS compared to placebo plus chemotherapy. At the 2021 SABCS, researchers will provide final study results, including outcomes in subgroups of patients by additional combined positive score cutoffs.
Metformin trial: ‘This is it’
Dr. Arteaga highlighted CCTGMA.32 (abstract GS1-08), a phase 3 randomized, placebo-controlled adjuvant trial of the diabetes drug metformin versus placebo in early breast cancer. Results of the primary efficacy analysis of the trial will be presented at the meeting.
The Canadian-led study seeks to determine if metformin can decrease breast cancer cell growth and work with cancer therapies to prevent disease recurrence. The study design calls for patients to take twice-daily oral metformin or placebo pills for up to 5 years in the absence of disease progression.
The primary outcome of the 3,500-plus patient trial is invasive disease-free survival in hormone receptor (ER and PgR) negative and positive (ER and/or PgR) subgroups.
“Metformin has actually been associated with improved survival [in breast cancer] in patients on chemotherapy. But we don’t know exactly how,” he said. “There’s never been a head-to-head comparison in the adjuvant setting [before]. This is it.”
TKI for breast cancer with brain mets
The SABCS codirector spotlighted an updated overall survival analysis of the randomized phase 3 PHOEBE trial (abstract GS3-02).
Previous research confirmed the superiority of pyrotinib, a novel TKI targeting HER1, HER2, and HER4, over lapatinib when given in combination with capecitabine in HER2-positive metastatic breast cancer.
In the United States, the lapatinib-capecitabine combination is “mostly used” in patients with HER2 metastatic disease and brain metastases who also undergo stereotactic radiation, Dr. Arteaga said.
This use has continued despite groundbreaking results from the HER2CLIMB trial, featuring the TKI tucatinib, he said.
As reported last year, adding tucatinib to trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases increased median overall survival from 12 months to 18.1 months. The results were called the first of their kind at that time.
The pyrotinib study may matter to American clinicians because pyrotinib is used mostly in China, not the United States, and this analysis suggests that pyrotinib could be part of the armamentarium in the United States, alongside tucatinib.
TKIs are like Coke and Pepsi, Dr. Arteaga said: “Similar but not identical.” Therefore, it is worth taking a look at the new study, he said. “There may be some benefit in having more than one [TKI] in the therapeutic armamentarium.”
Dr. Arteaga receives or has received grant support from Pfizer and Lilly and serves or has served in a scientific advisory role with Novartis, Lilly, TAIHO Oncology, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, and the Susan G. Komen Foundation. He also holds minor stock options from Provista.
A version of this article first appeared on Medscape.com.
FROM SABCS 2021
Pfizer COVID vaccine is 100% effective in adolescents: Study
Pfizer announced on Nov. 22 that its COVID-19 vaccine provided long-term protection against the virus in a late-stage clinical trial among adolescents ages 12-15.
A two-dose series was 100% effective against COVID-19, which was measured between 7 days and 4 months after the second dose.
“As the global health community works to increase the number of vaccinated people around the world, these additional data provide further confidence in our vaccine safety and effectiveness profile in adolescents,” Albert Bourla, PhD, chairman and CEO of Pfizer, said in a statement.
The clinical trial researchers found no serious safety concerns while following patients for 6 months. The adverse events were consistent with other clinical safety data for the vaccine, the company said.
Pfizer will incorporate the data into its submissions for full regulatory approval of the vaccine for ages 12-15 in the United States and worldwide.
The company will request clearance for a 30-mcg dose of the vaccines for ages 12 and older. The shot received FDA emergency use authorization for ages 12-15 in May and full approval for ages 16 and older in August.
The study included 2,228 clinical trial participants who were monitored between November 2020 and September 2021. There were 30 confirmed symptomatic cases of COVID-19 in the placebo group that didn’t receive the vaccine and 0 COVID-19 cases among the vaccinated group.
The efficacy was consistently high across gender, race, ethnicity, and health conditions, the company said.
“This is especially important as we see rates of COVID-19 climbing in this age group in some regions, while vaccine uptake has slowed,” Mr. Bourla said. “We look forward to sharing these data with the FDA and other regulators.”
A version of this article first appeared on WebMD.com.
Pfizer announced on Nov. 22 that its COVID-19 vaccine provided long-term protection against the virus in a late-stage clinical trial among adolescents ages 12-15.
A two-dose series was 100% effective against COVID-19, which was measured between 7 days and 4 months after the second dose.
“As the global health community works to increase the number of vaccinated people around the world, these additional data provide further confidence in our vaccine safety and effectiveness profile in adolescents,” Albert Bourla, PhD, chairman and CEO of Pfizer, said in a statement.
The clinical trial researchers found no serious safety concerns while following patients for 6 months. The adverse events were consistent with other clinical safety data for the vaccine, the company said.
Pfizer will incorporate the data into its submissions for full regulatory approval of the vaccine for ages 12-15 in the United States and worldwide.
The company will request clearance for a 30-mcg dose of the vaccines for ages 12 and older. The shot received FDA emergency use authorization for ages 12-15 in May and full approval for ages 16 and older in August.
The study included 2,228 clinical trial participants who were monitored between November 2020 and September 2021. There were 30 confirmed symptomatic cases of COVID-19 in the placebo group that didn’t receive the vaccine and 0 COVID-19 cases among the vaccinated group.
The efficacy was consistently high across gender, race, ethnicity, and health conditions, the company said.
“This is especially important as we see rates of COVID-19 climbing in this age group in some regions, while vaccine uptake has slowed,” Mr. Bourla said. “We look forward to sharing these data with the FDA and other regulators.”
A version of this article first appeared on WebMD.com.
Pfizer announced on Nov. 22 that its COVID-19 vaccine provided long-term protection against the virus in a late-stage clinical trial among adolescents ages 12-15.
A two-dose series was 100% effective against COVID-19, which was measured between 7 days and 4 months after the second dose.
“As the global health community works to increase the number of vaccinated people around the world, these additional data provide further confidence in our vaccine safety and effectiveness profile in adolescents,” Albert Bourla, PhD, chairman and CEO of Pfizer, said in a statement.
The clinical trial researchers found no serious safety concerns while following patients for 6 months. The adverse events were consistent with other clinical safety data for the vaccine, the company said.
Pfizer will incorporate the data into its submissions for full regulatory approval of the vaccine for ages 12-15 in the United States and worldwide.
The company will request clearance for a 30-mcg dose of the vaccines for ages 12 and older. The shot received FDA emergency use authorization for ages 12-15 in May and full approval for ages 16 and older in August.
The study included 2,228 clinical trial participants who were monitored between November 2020 and September 2021. There were 30 confirmed symptomatic cases of COVID-19 in the placebo group that didn’t receive the vaccine and 0 COVID-19 cases among the vaccinated group.
The efficacy was consistently high across gender, race, ethnicity, and health conditions, the company said.
“This is especially important as we see rates of COVID-19 climbing in this age group in some regions, while vaccine uptake has slowed,” Mr. Bourla said. “We look forward to sharing these data with the FDA and other regulators.”
A version of this article first appeared on WebMD.com.
Risk for breast cancer recurrence persists past 30 years
The data come from a Danish study involving 20,315 women who were treated for early operable breast cancer between 1987 and 2004, all of whom were disease-free at 10 years.
Further follow-up showed that 2,595 women had a breast cancer recurrence more than 10 years after their primary diagnosis.
The cumulative incidence of recurrence was 8.5% at 15 years; 12.5% at 20 years; 15.2% at 25 years, and 16.6% at 32 years.
Recurrence risk was greatest early in the study period.
Women who had primary tumors larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were at higher risk for late recurrence.
“Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches,” said the investigators, led by Rikke Pedersen, MD, a PhD candidate in epidemiology at Aarhus University Hospital, Denmark.
“Our observed high cumulative incidence of late breast cancer recurrence is a concern given the increasing prevalence of long-term survivors.” Among other things, a new model to better select women for prolonged surveillance is needed, they said.
The new findings were published online Nov. 8 in the Journal of the National Cancer Institute (NCI).
This study confirms previous investigations, but it is the first to report that breast cancer can recur more than 30 years after diagnosis, note the authors of an accompanying editorial, Serban Negoita, MD, DrPH, and Esmeralda Ramirez-Peña, PhD, MPH, both from the National Cancer Institute.
The caveat is that treatment has evolved considerably since the women in the study were diagnosed, so the prognostic value of the findings with current treatment regimens is uncertain, they note. Some studies haven’t found a recurrence benefit for aggressive upfront treatment, but those studies had shorter follow-ups.
Research into the issue is “increasingly important” to guide clinical management and counsel women who are living longer after their primary diagnosis, they comment.
Further details from the study
Data for the study came from the Danish Breast Cancer Group clinical database and other national databases. The researchers focused on women who were disease-free at 10 years after their primary diagnosis, which was stage I or II disease. Median age was 55 years.
Cumulative incidence for breast cancer recurrence was highest for grade 1 tumors with four or more positive lymph nodes (37.9% 10-25 years after the primary diagnosis) and was lowest for patients with grade 3 disease and no involved lymph nodes (7.5%).
The finding of higher recurrence incidence with lower grade tumors goes against some previous reports, the researchers commented. It may be that some tumors considered lower risk decades ago, and treated accordingly, would be considered higher risk in more recent times.
The cumulative incidence of late recurrence was also higher in younger patients and those treated with breast-conserving surgery instead of mastectomy, the team reported.
Adjusted hazard ratios followed the incidence trends, with higher hazards of recurrence for women diagnosed before age 40 as well as those who had breast-conserving surgery, four or more positive lymph nodes, and primary tumors 20 mm or more across.
The work was funded by the Danish Cancer Society and Aarhus University. Lead author Dr. Pedersen reports no disclosures, but coauthors report ties to Amgen, Novo Nordisk, Roche, and other companies. The editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The data come from a Danish study involving 20,315 women who were treated for early operable breast cancer between 1987 and 2004, all of whom were disease-free at 10 years.
Further follow-up showed that 2,595 women had a breast cancer recurrence more than 10 years after their primary diagnosis.
The cumulative incidence of recurrence was 8.5% at 15 years; 12.5% at 20 years; 15.2% at 25 years, and 16.6% at 32 years.
Recurrence risk was greatest early in the study period.
Women who had primary tumors larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were at higher risk for late recurrence.
“Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches,” said the investigators, led by Rikke Pedersen, MD, a PhD candidate in epidemiology at Aarhus University Hospital, Denmark.
“Our observed high cumulative incidence of late breast cancer recurrence is a concern given the increasing prevalence of long-term survivors.” Among other things, a new model to better select women for prolonged surveillance is needed, they said.
The new findings were published online Nov. 8 in the Journal of the National Cancer Institute (NCI).
This study confirms previous investigations, but it is the first to report that breast cancer can recur more than 30 years after diagnosis, note the authors of an accompanying editorial, Serban Negoita, MD, DrPH, and Esmeralda Ramirez-Peña, PhD, MPH, both from the National Cancer Institute.
The caveat is that treatment has evolved considerably since the women in the study were diagnosed, so the prognostic value of the findings with current treatment regimens is uncertain, they note. Some studies haven’t found a recurrence benefit for aggressive upfront treatment, but those studies had shorter follow-ups.
Research into the issue is “increasingly important” to guide clinical management and counsel women who are living longer after their primary diagnosis, they comment.
Further details from the study
Data for the study came from the Danish Breast Cancer Group clinical database and other national databases. The researchers focused on women who were disease-free at 10 years after their primary diagnosis, which was stage I or II disease. Median age was 55 years.
Cumulative incidence for breast cancer recurrence was highest for grade 1 tumors with four or more positive lymph nodes (37.9% 10-25 years after the primary diagnosis) and was lowest for patients with grade 3 disease and no involved lymph nodes (7.5%).
The finding of higher recurrence incidence with lower grade tumors goes against some previous reports, the researchers commented. It may be that some tumors considered lower risk decades ago, and treated accordingly, would be considered higher risk in more recent times.
The cumulative incidence of late recurrence was also higher in younger patients and those treated with breast-conserving surgery instead of mastectomy, the team reported.
Adjusted hazard ratios followed the incidence trends, with higher hazards of recurrence for women diagnosed before age 40 as well as those who had breast-conserving surgery, four or more positive lymph nodes, and primary tumors 20 mm or more across.
The work was funded by the Danish Cancer Society and Aarhus University. Lead author Dr. Pedersen reports no disclosures, but coauthors report ties to Amgen, Novo Nordisk, Roche, and other companies. The editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The data come from a Danish study involving 20,315 women who were treated for early operable breast cancer between 1987 and 2004, all of whom were disease-free at 10 years.
Further follow-up showed that 2,595 women had a breast cancer recurrence more than 10 years after their primary diagnosis.
The cumulative incidence of recurrence was 8.5% at 15 years; 12.5% at 20 years; 15.2% at 25 years, and 16.6% at 32 years.
Recurrence risk was greatest early in the study period.
Women who had primary tumors larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were at higher risk for late recurrence.
“Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches,” said the investigators, led by Rikke Pedersen, MD, a PhD candidate in epidemiology at Aarhus University Hospital, Denmark.
“Our observed high cumulative incidence of late breast cancer recurrence is a concern given the increasing prevalence of long-term survivors.” Among other things, a new model to better select women for prolonged surveillance is needed, they said.
The new findings were published online Nov. 8 in the Journal of the National Cancer Institute (NCI).
This study confirms previous investigations, but it is the first to report that breast cancer can recur more than 30 years after diagnosis, note the authors of an accompanying editorial, Serban Negoita, MD, DrPH, and Esmeralda Ramirez-Peña, PhD, MPH, both from the National Cancer Institute.
The caveat is that treatment has evolved considerably since the women in the study were diagnosed, so the prognostic value of the findings with current treatment regimens is uncertain, they note. Some studies haven’t found a recurrence benefit for aggressive upfront treatment, but those studies had shorter follow-ups.
Research into the issue is “increasingly important” to guide clinical management and counsel women who are living longer after their primary diagnosis, they comment.
Further details from the study
Data for the study came from the Danish Breast Cancer Group clinical database and other national databases. The researchers focused on women who were disease-free at 10 years after their primary diagnosis, which was stage I or II disease. Median age was 55 years.
Cumulative incidence for breast cancer recurrence was highest for grade 1 tumors with four or more positive lymph nodes (37.9% 10-25 years after the primary diagnosis) and was lowest for patients with grade 3 disease and no involved lymph nodes (7.5%).
The finding of higher recurrence incidence with lower grade tumors goes against some previous reports, the researchers commented. It may be that some tumors considered lower risk decades ago, and treated accordingly, would be considered higher risk in more recent times.
The cumulative incidence of late recurrence was also higher in younger patients and those treated with breast-conserving surgery instead of mastectomy, the team reported.
Adjusted hazard ratios followed the incidence trends, with higher hazards of recurrence for women diagnosed before age 40 as well as those who had breast-conserving surgery, four or more positive lymph nodes, and primary tumors 20 mm or more across.
The work was funded by the Danish Cancer Society and Aarhus University. Lead author Dr. Pedersen reports no disclosures, but coauthors report ties to Amgen, Novo Nordisk, Roche, and other companies. The editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Endoscopic resection of esophageal cancer requires long-term post-op surveillance
LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.
Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.
“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”
To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.
After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.
CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.
Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.
“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”
Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.
“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”
Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.
“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”
The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.
“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”
The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.
LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.
Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.
“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”
To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.
After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.
CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.
Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.
“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”
Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.
“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”
Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.
“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”
The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.
“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”
The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.
LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.
Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.
“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”
To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.
After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.
CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.
Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.
“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”
Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.
“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”
Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.
“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”
The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.
“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”
The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.
FROM ACG 2021