SGO Annual Meeting on Women's Cancer 2016

SAN DIEGO – Bilateral sentinel lymph node biopsy alone is a safe alternative to bilateral pelvic lymphadenectomy for stage I cervical cancer and might reduce morbidity, results from an observational study suggest.

“Prior studies have shown detection rates for sentinel lymph nodes and sensitivity for metastases of approximately 95% for cervical tumors less than 2 cm,” Dr. Genevieve K. Lennox said at the annual meeting of the Society of Gynecologic Oncology. “To our knowledge, ours is the first study specifically investigating the long-term outcomes for patients who have had bilateral sentinel lymph node biopsy alone for lymph node assessment in stage I cervical cancer.”

Dr. Lennox, a gynecologic oncology fellow in the department of ob.gyn. at the University of Toronto, and her associates used the university’s prospective cervical cancer database to identify 1,188 patients with stage IA/IB cervical cancer with negative lymph nodes on pathology after primary surgery with either bilateral pelvic lymphadenectomy (BPLND) or bilateral sentinel lymph node biopsy (BSLNB). They used Wilcoxon rank sum, chi square, and Fisher’s exact tests to compare the two groups, and a Cox proportional hazards model to identify predictors of recurrence-free survival.

The researchers observed no differences in recurrence-free survival between BPLND and BSLNB at 2 years (95% vs. 97%, respectively) or at 5 years (92% vs. 93%), nor in tumor size, histology, depth of invasion, intra-operative complications, or short-term morbidity. BPLND was, however, associated with increased surgical time (2.8 vs. 2 hours for BSLNB; P less than .001), blood loss (500 mL vs. 100 mL; P less than .001), transfusion (23% vs. 0%; P less than .001), and postoperative infection (11% vs. 0%; P = .001). Age, surgical date, stage, lymphovascular space invasion, and radicality of surgery differed between groups, she reported.

After controlling for confounders on multivariable cox regression analysis, only tumor size, lymphovascular space invasion, and histology were prognostic for recurrence-free survival, but mode of lymph node assessment was not.

“Seeing the data, it struck me how much less invasive the treatment of early cervical cancer has become over the past 20 years,” Dr. Lennox said. “Based on our data, it appears that bilateral sentinel lymph node biopsy alone is a safe alternative to bilateral pelvic lymphadenectomy for stage I cervical cancer and might reduce morbidity.”

She acknowledged certain limitations of the study, including its observational design and low recurrence rate. “However, to conduct a noninferiority trial with a 3% margin, assuming a 5-year recurrence rate of 7% in the pelvic lymphadenectomy group and 10% in the sentinel lymph node biopsy group, would require approximately 1,400 patients,” Dr. Lennox noted. “Since such a study is not feasible, we will have to continue accumulating data from prospective observational studies to inform decision making about the use of the sentinel lymph node strategy in cervical cancer.”

[email protected]

SAN DIEGO – Bilateral sentinel lymph node biopsy alone is a safe alternative to bilateral pelvic lymphadenectomy for stage I cervical cancer and might reduce morbidity, results from an observational study suggest.

“Prior studies have shown detection rates for sentinel lymph nodes and sensitivity for metastases of approximately 95% for cervical tumors less than 2 cm,” Dr. Genevieve K. Lennox said at the annual meeting of the Society of Gynecologic Oncology. “To our knowledge, ours is the first study specifically investigating the long-term outcomes for patients who have had bilateral sentinel lymph node biopsy alone for lymph node assessment in stage I cervical cancer.”

Dr. Lennox, a gynecologic oncology fellow in the department of ob.gyn. at the University of Toronto, and her associates used the university’s prospective cervical cancer database to identify 1,188 patients with stage IA/IB cervical cancer with negative lymph nodes on pathology after primary surgery with either bilateral pelvic lymphadenectomy (BPLND) or bilateral sentinel lymph node biopsy (BSLNB). They used Wilcoxon rank sum, chi square, and Fisher’s exact tests to compare the two groups, and a Cox proportional hazards model to identify predictors of recurrence-free survival.

The researchers observed no differences in recurrence-free survival between BPLND and BSLNB at 2 years (95% vs. 97%, respectively) or at 5 years (92% vs. 93%), nor in tumor size, histology, depth of invasion, intra-operative complications, or short-term morbidity. BPLND was, however, associated with increased surgical time (2.8 vs. 2 hours for BSLNB; P less than .001), blood loss (500 mL vs. 100 mL; P less than .001), transfusion (23% vs. 0%; P less than .001), and postoperative infection (11% vs. 0%; P = .001). Age, surgical date, stage, lymphovascular space invasion, and radicality of surgery differed between groups, she reported.

After controlling for confounders on multivariable cox regression analysis, only tumor size, lymphovascular space invasion, and histology were prognostic for recurrence-free survival, but mode of lymph node assessment was not.

“Seeing the data, it struck me how much less invasive the treatment of early cervical cancer has become over the past 20 years,” Dr. Lennox said. “Based on our data, it appears that bilateral sentinel lymph node biopsy alone is a safe alternative to bilateral pelvic lymphadenectomy for stage I cervical cancer and might reduce morbidity.”

She acknowledged certain limitations of the study, including its observational design and low recurrence rate. “However, to conduct a noninferiority trial with a 3% margin, assuming a 5-year recurrence rate of 7% in the pelvic lymphadenectomy group and 10% in the sentinel lymph node biopsy group, would require approximately 1,400 patients,” Dr. Lennox noted. “Since such a study is not feasible, we will have to continue accumulating data from prospective observational studies to inform decision making about the use of the sentinel lymph node strategy in cervical cancer.”

[email protected]

SAN DIEGO – Bilateral sentinel lymph node biopsy alone is a safe alternative to bilateral pelvic lymphadenectomy for stage I cervical cancer and might reduce morbidity, results from an observational study suggest.

“Prior studies have shown detection rates for sentinel lymph nodes and sensitivity for metastases of approximately 95% for cervical tumors less than 2 cm,” Dr. Genevieve K. Lennox said at the annual meeting of the Society of Gynecologic Oncology. “To our knowledge, ours is the first study specifically investigating the long-term outcomes for patients who have had bilateral sentinel lymph node biopsy alone for lymph node assessment in stage I cervical cancer.”

Dr. Lennox, a gynecologic oncology fellow in the department of ob.gyn. at the University of Toronto, and her associates used the university’s prospective cervical cancer database to identify 1,188 patients with stage IA/IB cervical cancer with negative lymph nodes on pathology after primary surgery with either bilateral pelvic lymphadenectomy (BPLND) or bilateral sentinel lymph node biopsy (BSLNB). They used Wilcoxon rank sum, chi square, and Fisher’s exact tests to compare the two groups, and a Cox proportional hazards model to identify predictors of recurrence-free survival.

The researchers observed no differences in recurrence-free survival between BPLND and BSLNB at 2 years (95% vs. 97%, respectively) or at 5 years (92% vs. 93%), nor in tumor size, histology, depth of invasion, intra-operative complications, or short-term morbidity. BPLND was, however, associated with increased surgical time (2.8 vs. 2 hours for BSLNB; P less than .001), blood loss (500 mL vs. 100 mL; P less than .001), transfusion (23% vs. 0%; P less than .001), and postoperative infection (11% vs. 0%; P = .001). Age, surgical date, stage, lymphovascular space invasion, and radicality of surgery differed between groups, she reported.

After controlling for confounders on multivariable cox regression analysis, only tumor size, lymphovascular space invasion, and histology were prognostic for recurrence-free survival, but mode of lymph node assessment was not.

“Seeing the data, it struck me how much less invasive the treatment of early cervical cancer has become over the past 20 years,” Dr. Lennox said. “Based on our data, it appears that bilateral sentinel lymph node biopsy alone is a safe alternative to bilateral pelvic lymphadenectomy for stage I cervical cancer and might reduce morbidity.”

She acknowledged certain limitations of the study, including its observational design and low recurrence rate. “However, to conduct a noninferiority trial with a 3% margin, assuming a 5-year recurrence rate of 7% in the pelvic lymphadenectomy group and 10% in the sentinel lymph node biopsy group, would require approximately 1,400 patients,” Dr. Lennox noted. “Since such a study is not feasible, we will have to continue accumulating data from prospective observational studies to inform decision making about the use of the sentinel lymph node strategy in cervical cancer.”

[email protected]

SAN DIEGO – There are “tantalizing” trends toward reduced ovarian cancer deaths with annual cancer antigen 125 screening in a United Kingdom trial involving about 200,000, average-risk postmenopausal women, according to investigator Dr. Ian Jacobs of the University of New South Wales, Sydney.

From 2001-2005, a quarter of the women were randomized to annual cancer antigen 125 (CA-125) screening, with ultrasound follow-up and oncology referral as indicated; a quarter to annual transvaginal ultrasound screening and referral; and a half to no screening, as a control. Screening ended in Dec. 2011 (Lancet. 2016 Mar 5;387(10022):945-56).

Frontline Medical News/M. Alexander Otto

At a median follow-up of 11.1 years, there was a nonsignificant mortality reduction of 15% (95% confidence interval, –3 to 30; P = .10) with CA-125/ultrasound multimodal screening (MMS), and 11% reduction (95% CI, –7 to 27; P = .21) with ultrasound screening. A second analysis suggested a greater, though still nonsignificant, benefit after 7 years of screening, “which is typical of cancer screening trials,” Dr. Jacobs said at the annual meeting of the Society of Gynecologic Oncology.

When women who entered the trial with ovarian cancer were excluded, there was a statistically significant 20% (95% CI, –2 to 40) overall mortality reduction and 28% reduction (95% CI, –3 to 49) after year 7 in the MMS group, compared with controls (P = .021).

“The performance criteria are good” for MMS, “and the mortality data are somewhat persuasive, but not quite there yet. We need to continue follow-up for an additional 2-3 years. If the mortality reduction pans out, the health economics are probably similar to breast cancer screening. My hope is that by about 2020, we will be including ovarian cancer screening alongside breast and cervical cancer screening,” Dr. Jacobs said.

The study excluded women with previous ovarian malignancy and two or more first degree relatives with ovarian cancer. CA-125 was interpreted with the risk of ovarian cancer algorithm, which considers changes over time, with increases indicating potential problems.

Ovarian cancer was diagnosed in 338 (0.7%) women in the MMS arm, 314 (0.6%) women in the ultrasound arm; and 630 (0.6%) women in the control group. Mortality was lowest in the MMS group, with 148 (0.29%) succumbing to the disease, versus 154 (0.30%) in the ultrasound and 347 (0.34%) in the control arms.

MMS outperformed ultrasound screening on every measure, with a 25% positive predictive value, 448 false-positive operations with 345,990 screenings, one significant compilation per 23,066 screens, and compliance of 81%. MMS was also more likely to detect earlier stage disease.

With liquid biopsy and other potential screening tests coming online, “I’m pretty sure that in due course we will not be using just one test” for screening. “The dream scenario is that we end up with a panel of tests which could reduce mortality even more,” Dr. Jacobs said.

[email protected]

SAN DIEGO – There are “tantalizing” trends toward reduced ovarian cancer deaths with annual cancer antigen 125 screening in a United Kingdom trial involving about 200,000, average-risk postmenopausal women, according to investigator Dr. Ian Jacobs of the University of New South Wales, Sydney.

From 2001-2005, a quarter of the women were randomized to annual cancer antigen 125 (CA-125) screening, with ultrasound follow-up and oncology referral as indicated; a quarter to annual transvaginal ultrasound screening and referral; and a half to no screening, as a control. Screening ended in Dec. 2011 (Lancet. 2016 Mar 5;387(10022):945-56).

Frontline Medical News/M. Alexander Otto

At a median follow-up of 11.1 years, there was a nonsignificant mortality reduction of 15% (95% confidence interval, –3 to 30; P = .10) with CA-125/ultrasound multimodal screening (MMS), and 11% reduction (95% CI, –7 to 27; P = .21) with ultrasound screening. A second analysis suggested a greater, though still nonsignificant, benefit after 7 years of screening, “which is typical of cancer screening trials,” Dr. Jacobs said at the annual meeting of the Society of Gynecologic Oncology.

When women who entered the trial with ovarian cancer were excluded, there was a statistically significant 20% (95% CI, –2 to 40) overall mortality reduction and 28% reduction (95% CI, –3 to 49) after year 7 in the MMS group, compared with controls (P = .021).

“The performance criteria are good” for MMS, “and the mortality data are somewhat persuasive, but not quite there yet. We need to continue follow-up for an additional 2-3 years. If the mortality reduction pans out, the health economics are probably similar to breast cancer screening. My hope is that by about 2020, we will be including ovarian cancer screening alongside breast and cervical cancer screening,” Dr. Jacobs said.

The study excluded women with previous ovarian malignancy and two or more first degree relatives with ovarian cancer. CA-125 was interpreted with the risk of ovarian cancer algorithm, which considers changes over time, with increases indicating potential problems.

Ovarian cancer was diagnosed in 338 (0.7%) women in the MMS arm, 314 (0.6%) women in the ultrasound arm; and 630 (0.6%) women in the control group. Mortality was lowest in the MMS group, with 148 (0.29%) succumbing to the disease, versus 154 (0.30%) in the ultrasound and 347 (0.34%) in the control arms.

MMS outperformed ultrasound screening on every measure, with a 25% positive predictive value, 448 false-positive operations with 345,990 screenings, one significant compilation per 23,066 screens, and compliance of 81%. MMS was also more likely to detect earlier stage disease.

With liquid biopsy and other potential screening tests coming online, “I’m pretty sure that in due course we will not be using just one test” for screening. “The dream scenario is that we end up with a panel of tests which could reduce mortality even more,” Dr. Jacobs said.

[email protected]

SAN DIEGO – There are “tantalizing” trends toward reduced ovarian cancer deaths with annual cancer antigen 125 screening in a United Kingdom trial involving about 200,000, average-risk postmenopausal women, according to investigator Dr. Ian Jacobs of the University of New South Wales, Sydney.

From 2001-2005, a quarter of the women were randomized to annual cancer antigen 125 (CA-125) screening, with ultrasound follow-up and oncology referral as indicated; a quarter to annual transvaginal ultrasound screening and referral; and a half to no screening, as a control. Screening ended in Dec. 2011 (Lancet. 2016 Mar 5;387(10022):945-56).

Frontline Medical News/M. Alexander Otto

At a median follow-up of 11.1 years, there was a nonsignificant mortality reduction of 15% (95% confidence interval, –3 to 30; P = .10) with CA-125/ultrasound multimodal screening (MMS), and 11% reduction (95% CI, –7 to 27; P = .21) with ultrasound screening. A second analysis suggested a greater, though still nonsignificant, benefit after 7 years of screening, “which is typical of cancer screening trials,” Dr. Jacobs said at the annual meeting of the Society of Gynecologic Oncology.

When women who entered the trial with ovarian cancer were excluded, there was a statistically significant 20% (95% CI, –2 to 40) overall mortality reduction and 28% reduction (95% CI, –3 to 49) after year 7 in the MMS group, compared with controls (P = .021).

“The performance criteria are good” for MMS, “and the mortality data are somewhat persuasive, but not quite there yet. We need to continue follow-up for an additional 2-3 years. If the mortality reduction pans out, the health economics are probably similar to breast cancer screening. My hope is that by about 2020, we will be including ovarian cancer screening alongside breast and cervical cancer screening,” Dr. Jacobs said.

The study excluded women with previous ovarian malignancy and two or more first degree relatives with ovarian cancer. CA-125 was interpreted with the risk of ovarian cancer algorithm, which considers changes over time, with increases indicating potential problems.

Ovarian cancer was diagnosed in 338 (0.7%) women in the MMS arm, 314 (0.6%) women in the ultrasound arm; and 630 (0.6%) women in the control group. Mortality was lowest in the MMS group, with 148 (0.29%) succumbing to the disease, versus 154 (0.30%) in the ultrasound and 347 (0.34%) in the control arms.

MMS outperformed ultrasound screening on every measure, with a 25% positive predictive value, 448 false-positive operations with 345,990 screenings, one significant compilation per 23,066 screens, and compliance of 81%. MMS was also more likely to detect earlier stage disease.

With liquid biopsy and other potential screening tests coming online, “I’m pretty sure that in due course we will not be using just one test” for screening. “The dream scenario is that we end up with a panel of tests which could reduce mortality even more,” Dr. Jacobs said.

[email protected]

SAN DIEGO – The presence of lymphovascular space invasion in the setting of early-stage endometrial cancer is a more potent independent predictor of associated pelvic lymph node metastases than previously recognized, Dr. Soledad Jorge reported at the annual meeting of the Society of Gynecologic Oncology.

Indeed, she found in her large, population-based study that lymphovascular space invasion (LVSI) was the strongest predictor of nodal disease, even more robust than tumor grade. LVSI also was associated with a 1.92-fold increased risk of mortality at 45 months’ follow-up after adjustment for the presence of lymph node metastases.

Bruce Jancin/Frontline Medical News

This was a study of 25,907 women with surgically staged endometrioid adenocarcinoma of the endometrium who underwent hysterectomy and lymphadenectomy during 2010-2012 and were registered in the National Cancer Data Base. Seventy-two percent of them had T1A disease, defined by less than 50% myometrial invasion, while the remaining 28% had T1B disease with greater than 50% myoinvasion, according to Dr. Jorge of Columbia University in New York.

LVSI was present in 15.2% of the women. Lymph node metastases were detected in 5% of the overall study population. Twenty-one percent of women with LVSI had positive pelvic lymph nodes, compared with just 2.1% of patients without LVSI, she said.

When patients were stratified by tumor depth and invasion, LVSI was independently associated with a 3- to 16-fold increased risk of nodal metastases. In a more comprehensive multivariate regression analysis adjusted for age, tumor stage and grade, and other demographic and clinical factors, the relative risk of lymph node metastases in patients with T1A disease and LVSI was increased 9.2-fold, compared with that of patients with no LVSI. Patients with T1B disease and LVSI were at 4.6-fold greater risk for lymph node metastases than were T1B patients without LVSI, Dr. Jorge said.

LVSI was associated with significantly reduced survival out to 45 months in all patient subgroups except those having Stage IA, grade 1 tumors.

Dr. Jorge reported having no financial conflicts regarding this study, which was conducted free of commercial support.

[email protected]

SAN DIEGO – The presence of lymphovascular space invasion in the setting of early-stage endometrial cancer is a more potent independent predictor of associated pelvic lymph node metastases than previously recognized, Dr. Soledad Jorge reported at the annual meeting of the Society of Gynecologic Oncology.

Indeed, she found in her large, population-based study that lymphovascular space invasion (LVSI) was the strongest predictor of nodal disease, even more robust than tumor grade. LVSI also was associated with a 1.92-fold increased risk of mortality at 45 months’ follow-up after adjustment for the presence of lymph node metastases.

Bruce Jancin/Frontline Medical News

This was a study of 25,907 women with surgically staged endometrioid adenocarcinoma of the endometrium who underwent hysterectomy and lymphadenectomy during 2010-2012 and were registered in the National Cancer Data Base. Seventy-two percent of them had T1A disease, defined by less than 50% myometrial invasion, while the remaining 28% had T1B disease with greater than 50% myoinvasion, according to Dr. Jorge of Columbia University in New York.

LVSI was present in 15.2% of the women. Lymph node metastases were detected in 5% of the overall study population. Twenty-one percent of women with LVSI had positive pelvic lymph nodes, compared with just 2.1% of patients without LVSI, she said.

When patients were stratified by tumor depth and invasion, LVSI was independently associated with a 3- to 16-fold increased risk of nodal metastases. In a more comprehensive multivariate regression analysis adjusted for age, tumor stage and grade, and other demographic and clinical factors, the relative risk of lymph node metastases in patients with T1A disease and LVSI was increased 9.2-fold, compared with that of patients with no LVSI. Patients with T1B disease and LVSI were at 4.6-fold greater risk for lymph node metastases than were T1B patients without LVSI, Dr. Jorge said.

LVSI was associated with significantly reduced survival out to 45 months in all patient subgroups except those having Stage IA, grade 1 tumors.

Dr. Jorge reported having no financial conflicts regarding this study, which was conducted free of commercial support.

[email protected]

SAN DIEGO – The presence of lymphovascular space invasion in the setting of early-stage endometrial cancer is a more potent independent predictor of associated pelvic lymph node metastases than previously recognized, Dr. Soledad Jorge reported at the annual meeting of the Society of Gynecologic Oncology.

Indeed, she found in her large, population-based study that lymphovascular space invasion (LVSI) was the strongest predictor of nodal disease, even more robust than tumor grade. LVSI also was associated with a 1.92-fold increased risk of mortality at 45 months’ follow-up after adjustment for the presence of lymph node metastases.

Bruce Jancin/Frontline Medical News

This was a study of 25,907 women with surgically staged endometrioid adenocarcinoma of the endometrium who underwent hysterectomy and lymphadenectomy during 2010-2012 and were registered in the National Cancer Data Base. Seventy-two percent of them had T1A disease, defined by less than 50% myometrial invasion, while the remaining 28% had T1B disease with greater than 50% myoinvasion, according to Dr. Jorge of Columbia University in New York.

LVSI was present in 15.2% of the women. Lymph node metastases were detected in 5% of the overall study population. Twenty-one percent of women with LVSI had positive pelvic lymph nodes, compared with just 2.1% of patients without LVSI, she said.

When patients were stratified by tumor depth and invasion, LVSI was independently associated with a 3- to 16-fold increased risk of nodal metastases. In a more comprehensive multivariate regression analysis adjusted for age, tumor stage and grade, and other demographic and clinical factors, the relative risk of lymph node metastases in patients with T1A disease and LVSI was increased 9.2-fold, compared with that of patients with no LVSI. Patients with T1B disease and LVSI were at 4.6-fold greater risk for lymph node metastases than were T1B patients without LVSI, Dr. Jorge said.

LVSI was associated with significantly reduced survival out to 45 months in all patient subgroups except those having Stage IA, grade 1 tumors.

Dr. Jorge reported having no financial conflicts regarding this study, which was conducted free of commercial support.

[email protected]

SAN DIEGO – Non-modifiable demographic, financial, and geographic factors impacted patient-reported satisfaction with the care women received at a gynecologic oncology clinic, a single-center study showed.

“This study agrees with previous work in other disciplines that patient satisfaction scores, at the initiation of care, are affected by non-modifiable patient and system factors such as the age of the patient or the size of the hospital,” lead study author Dr. Emma L. Barber said in an interview prior to the annual meeting of Society of Gynecologic Oncology where she was presenting the study.

Frontline Medical News/Doug Brunk

“The study is unique in that it is the first to examine this question specifically in gynecologic cancer patients in the outpatient setting. Cancer patients, and specifically gynecologic cancer patients, may have different perspectives on satisfaction with care than broader groups of patients, such as general internal medicine patients,” she said.

Dr. Barber, a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill, and her associates administered the Patient Satisfaction Questionnaire (PSQ-18) to 208 women seeking surgical management at the university’s gynecology clinic. The tool measures patient satisfaction in seven health care domains: general satisfaction, technical quality, interpersonal manner, communication, financial aspects, time spent with physicians, and accessibility on a five-point Likert scale. The researchers converted scores to “satisfied” versus “unsatisfied/equivocal” based on a cutoff of 3.5.

The median age of respondents was 58 years, their median PSQ-18 score was 70.5, 78% were white, 32% had some college/trade school education, and 43% were college graduates or had other advanced degrees. The majority of respondents (84%) had some private insurance, 9% had Medicaid/Medicare alone, and 7% were uninsured.

White patients had higher levels of patient satisfaction, compared with other minorities (86% vs. 65%; P less than .01), while uninsured patients had lower scores in the following domains of patient satisfaction, compared with their insured counterparts: interpersonal (60% vs. 83%; P = .02), financial (27% vs. 61%; P = .01), and accessibility (33% vs. 67%; P = .01). Increasing education was also associated with higher scores in the interpersonal and accessibility domains of patient satisfaction (P of .03 and .01, respectively). Multivariate regression analysis revealed that the strongest predictors of patient satisfaction were white race (adjusted OR 2.7) and each 20 minutes less traveled (adjusted OR of 1.2).

“Tertiary care facilities that serve heterogeneous populations and have large catchment areas can use this information to target improvement projects at specific domains of patient satisfaction,” Dr. Barber said. “However, given the association between non-modifiable factors and satisfaction, performance measures that use patient satisfaction scores based only on summed domain scores may be penalizing clinics for patient mix differences. Financially penalizing clinics that care for underserved patients may exacerbate healthcare disparities. Instead, a system of incentives for improvement may be more appropriate.”

She acknowledged certain limitations of the study, including its prospective, single-center design. “The results may not be generalizable to other institutions or practice settings. Additionally, we tested multiple hypotheses to examine the effects of various factors on the different domains of patient satisfaction. Thus, these results should be considered hypothesis generating and need to be confirmed in additional studies.”

[email protected]

SAN DIEGO – Non-modifiable demographic, financial, and geographic factors impacted patient-reported satisfaction with the care women received at a gynecologic oncology clinic, a single-center study showed.

“This study agrees with previous work in other disciplines that patient satisfaction scores, at the initiation of care, are affected by non-modifiable patient and system factors such as the age of the patient or the size of the hospital,” lead study author Dr. Emma L. Barber said in an interview prior to the annual meeting of Society of Gynecologic Oncology where she was presenting the study.

Frontline Medical News/Doug Brunk

“The study is unique in that it is the first to examine this question specifically in gynecologic cancer patients in the outpatient setting. Cancer patients, and specifically gynecologic cancer patients, may have different perspectives on satisfaction with care than broader groups of patients, such as general internal medicine patients,” she said.

Dr. Barber, a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill, and her associates administered the Patient Satisfaction Questionnaire (PSQ-18) to 208 women seeking surgical management at the university’s gynecology clinic. The tool measures patient satisfaction in seven health care domains: general satisfaction, technical quality, interpersonal manner, communication, financial aspects, time spent with physicians, and accessibility on a five-point Likert scale. The researchers converted scores to “satisfied” versus “unsatisfied/equivocal” based on a cutoff of 3.5.

The median age of respondents was 58 years, their median PSQ-18 score was 70.5, 78% were white, 32% had some college/trade school education, and 43% were college graduates or had other advanced degrees. The majority of respondents (84%) had some private insurance, 9% had Medicaid/Medicare alone, and 7% were uninsured.

White patients had higher levels of patient satisfaction, compared with other minorities (86% vs. 65%; P less than .01), while uninsured patients had lower scores in the following domains of patient satisfaction, compared with their insured counterparts: interpersonal (60% vs. 83%; P = .02), financial (27% vs. 61%; P = .01), and accessibility (33% vs. 67%; P = .01). Increasing education was also associated with higher scores in the interpersonal and accessibility domains of patient satisfaction (P of .03 and .01, respectively). Multivariate regression analysis revealed that the strongest predictors of patient satisfaction were white race (adjusted OR 2.7) and each 20 minutes less traveled (adjusted OR of 1.2).

“Tertiary care facilities that serve heterogeneous populations and have large catchment areas can use this information to target improvement projects at specific domains of patient satisfaction,” Dr. Barber said. “However, given the association between non-modifiable factors and satisfaction, performance measures that use patient satisfaction scores based only on summed domain scores may be penalizing clinics for patient mix differences. Financially penalizing clinics that care for underserved patients may exacerbate healthcare disparities. Instead, a system of incentives for improvement may be more appropriate.”

She acknowledged certain limitations of the study, including its prospective, single-center design. “The results may not be generalizable to other institutions or practice settings. Additionally, we tested multiple hypotheses to examine the effects of various factors on the different domains of patient satisfaction. Thus, these results should be considered hypothesis generating and need to be confirmed in additional studies.”

[email protected]

SAN DIEGO – Non-modifiable demographic, financial, and geographic factors impacted patient-reported satisfaction with the care women received at a gynecologic oncology clinic, a single-center study showed.

“This study agrees with previous work in other disciplines that patient satisfaction scores, at the initiation of care, are affected by non-modifiable patient and system factors such as the age of the patient or the size of the hospital,” lead study author Dr. Emma L. Barber said in an interview prior to the annual meeting of Society of Gynecologic Oncology where she was presenting the study.

Frontline Medical News/Doug Brunk

“The study is unique in that it is the first to examine this question specifically in gynecologic cancer patients in the outpatient setting. Cancer patients, and specifically gynecologic cancer patients, may have different perspectives on satisfaction with care than broader groups of patients, such as general internal medicine patients,” she said.

Dr. Barber, a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill, and her associates administered the Patient Satisfaction Questionnaire (PSQ-18) to 208 women seeking surgical management at the university’s gynecology clinic. The tool measures patient satisfaction in seven health care domains: general satisfaction, technical quality, interpersonal manner, communication, financial aspects, time spent with physicians, and accessibility on a five-point Likert scale. The researchers converted scores to “satisfied” versus “unsatisfied/equivocal” based on a cutoff of 3.5.

The median age of respondents was 58 years, their median PSQ-18 score was 70.5, 78% were white, 32% had some college/trade school education, and 43% were college graduates or had other advanced degrees. The majority of respondents (84%) had some private insurance, 9% had Medicaid/Medicare alone, and 7% were uninsured.

White patients had higher levels of patient satisfaction, compared with other minorities (86% vs. 65%; P less than .01), while uninsured patients had lower scores in the following domains of patient satisfaction, compared with their insured counterparts: interpersonal (60% vs. 83%; P = .02), financial (27% vs. 61%; P = .01), and accessibility (33% vs. 67%; P = .01). Increasing education was also associated with higher scores in the interpersonal and accessibility domains of patient satisfaction (P of .03 and .01, respectively). Multivariate regression analysis revealed that the strongest predictors of patient satisfaction were white race (adjusted OR 2.7) and each 20 minutes less traveled (adjusted OR of 1.2).

“Tertiary care facilities that serve heterogeneous populations and have large catchment areas can use this information to target improvement projects at specific domains of patient satisfaction,” Dr. Barber said. “However, given the association between non-modifiable factors and satisfaction, performance measures that use patient satisfaction scores based only on summed domain scores may be penalizing clinics for patient mix differences. Financially penalizing clinics that care for underserved patients may exacerbate healthcare disparities. Instead, a system of incentives for improvement may be more appropriate.”

She acknowledged certain limitations of the study, including its prospective, single-center design. “The results may not be generalizable to other institutions or practice settings. Additionally, we tested multiple hypotheses to examine the effects of various factors on the different domains of patient satisfaction. Thus, these results should be considered hypothesis generating and need to be confirmed in additional studies.”

[email protected]

SAN DIEGO – There is a survival benefit to debulking stage IIIC ovarian, fallopian tube, and peritoneal tumors down to 10mm or smaller in size, a single-center retrospective study demonstrated.

“You shouldn’t just relegate those patients [in whom] you can’t get a complete gross resection to neoadjuvant chemotherapy, because their median survival is going to generally be around 30-36 months,” Dr. Dennis S. Chi said in an interview in advance of the annual meeting of Society of Gynecologic Oncology. “But if you do a primary debulking and you get the volume of residual disease down to 10 mm or smaller in maximal diameter, the median survivals can be in the mid-40s to over 80 months.”

Dr. Chi, head of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center, New York, said that the current findings come at a time when the initial management of advanced ovarian cancer is in flux and is controversial. “For decades it used to be that the initial step was to do an operation and to do a primary debulking surgery,” he said. “But studies in the 1980s and 1990s showed that if you did primary debulking surgery and you did the standard surgery that gynecologic oncologists did at that time, greater than 50% of the time you would not do an operation that would result in an optimal debulking, where you get all or almost all of the visible cancer out.”

Two camps formed, he continued, one consisting of clinicians who believe “we need to do better surgery, or more comprehensive surgery,” and another group of clinicians who say, “Why don’t we treat with chemotherapy first for three treatments, and then do surgery? Maybe this will shrink the cancer and consequently improve the surgical outcome.’ Both camps agree that if you cannot get all the cancer out or almost all the cancer out, then you should start with chemotherapy first. The question then lies, what is the cut-off?”

In a study led by Dr. Chi and Dr. Vasileios Sioulas, the Senior International Gynecologic Oncology Fellow at Memorial Sloan Kettering Cancer Center, the authors set out to explore the effect of primary cytoreduction to minimal but gross residual disease in women with bulky stage IIIC ovarian/fallopian tube/primary peritoneal cancer. They retrospectively evaluated the records of 496 women who underwent primary debulking surgery at the cancer center between 2001 and 2010. Their median age was 62 years, the median operative time was 265 minutes, and 46% of the patients received at least one cycle of primary or consolidation intraperitoneal chemotherapy.

The researchers assigned patients to one of four groups based on reported gross residual disease. More than one-third (37%) had no gross residual disease (group 1); 26% had residual disease of 1-5 mm in diameter (group 2); 11% had residual disease of 6-10 mm in diameter (group 3), and 26% had residual disease that exceeded 10 mm in diameter (group 4). The median follow-up in the entire cohort was 53 months, the median progression-free survival was 18.6 months, and the median overall survival was 54.7 months. However, median progression-free survival and median overall survival varied significantly among the four assigned groups. It was 26.7 months for group 1, 20.7 months for group 2, 16.2 months for group 3, and 13.6 months for group 4 (P less than .001). At the same time, median overall survival was 83.4 months for group 1, 54.5 months for 2, 43.8 months for group 3, and 38.9 months for group 4 (P less than .001).

To be consistent with the vast majority of the existing literature, which used the cut-off of 10 mm to define optimal residual disease, Dr. Sioulas and his associates merged patients with residual disease 1-5 mm and 6-10 mm into one group and found that its median overall survival was 52.6 months. Patients with residual disease of 1-10 mm had significantly better overall survival, as compared to those with residual disease greater than 10 mm (P less than .001). Importantly, among the patients with residual disease of 1-10 mm, the administration of at least one cycle of primary intraperitoneal chemotherapy was associated with significantly prolonged overall survival, as compared to the sole use of intravenous chemotherapy. The median overall survival for those groups was 65.1 and 40.6 months, respectively (P = .002).

“I certainly believe neoadjuvant chemotherapy is the best approach in certain situations, but I don’t think it should be the knee-jerk reflex for all patients with advanced ovarian cancer,” Dr. Chi said. “I think that may be doing a disservice to many patients who could get a distinct prolongation of life and overall survival, or even cure, with a primary debulking surgery approach.”

He noted that ovarian cancer “goes where it wants to go. It doesn’t care what the training or surgical capabilities of the surgeon are. It’s going to go where it wants to go, so you can’t make the patient and the disease fit into your training skill set. You have to adapt your training skill set to the disease.”

The ideal study of this issue, Dr. Chi said, would “compare 400 or 500 patients with primary debulking and 400 or 500 patients who receive neoadjuvant chemotherapy to see which approach is better. There are two trials that have been done in Europe and have shown that it doesn’t matter, that the outcomes are the same whether you do primary debulking first or neoadjuvant chemotherapy first [see N. Engl. J. Med. 2010;363;943-53 and Lancet 2015;386:249-57]. Unfortunately, the survival outcomes in their primary debulking surgery arm were much lower as compared to other studies, especially those conducted in the United States. This highlights the importance of homogeneity in advanced surgical skills as a prerequisite before we draw definite conclusions about the survival outcomes after primary debulking surgery in patients with advanced disease.”

Dr. Chi acknowledged certain limitations of the study, including its retrospective design and the fact that surgeons at Memorial Sloan Kettering “are more willing, and have more support staff available, to perform comprehensive surgeries than at other centers.”

[email protected]

SAN DIEGO – There is a survival benefit to debulking stage IIIC ovarian, fallopian tube, and peritoneal tumors down to 10mm or smaller in size, a single-center retrospective study demonstrated.

“You shouldn’t just relegate those patients [in whom] you can’t get a complete gross resection to neoadjuvant chemotherapy, because their median survival is going to generally be around 30-36 months,” Dr. Dennis S. Chi said in an interview in advance of the annual meeting of Society of Gynecologic Oncology. “But if you do a primary debulking and you get the volume of residual disease down to 10 mm or smaller in maximal diameter, the median survivals can be in the mid-40s to over 80 months.”

Dr. Chi, head of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center, New York, said that the current findings come at a time when the initial management of advanced ovarian cancer is in flux and is controversial. “For decades it used to be that the initial step was to do an operation and to do a primary debulking surgery,” he said. “But studies in the 1980s and 1990s showed that if you did primary debulking surgery and you did the standard surgery that gynecologic oncologists did at that time, greater than 50% of the time you would not do an operation that would result in an optimal debulking, where you get all or almost all of the visible cancer out.”

Two camps formed, he continued, one consisting of clinicians who believe “we need to do better surgery, or more comprehensive surgery,” and another group of clinicians who say, “Why don’t we treat with chemotherapy first for three treatments, and then do surgery? Maybe this will shrink the cancer and consequently improve the surgical outcome.’ Both camps agree that if you cannot get all the cancer out or almost all the cancer out, then you should start with chemotherapy first. The question then lies, what is the cut-off?”

In a study led by Dr. Chi and Dr. Vasileios Sioulas, the Senior International Gynecologic Oncology Fellow at Memorial Sloan Kettering Cancer Center, the authors set out to explore the effect of primary cytoreduction to minimal but gross residual disease in women with bulky stage IIIC ovarian/fallopian tube/primary peritoneal cancer. They retrospectively evaluated the records of 496 women who underwent primary debulking surgery at the cancer center between 2001 and 2010. Their median age was 62 years, the median operative time was 265 minutes, and 46% of the patients received at least one cycle of primary or consolidation intraperitoneal chemotherapy.

The researchers assigned patients to one of four groups based on reported gross residual disease. More than one-third (37%) had no gross residual disease (group 1); 26% had residual disease of 1-5 mm in diameter (group 2); 11% had residual disease of 6-10 mm in diameter (group 3), and 26% had residual disease that exceeded 10 mm in diameter (group 4). The median follow-up in the entire cohort was 53 months, the median progression-free survival was 18.6 months, and the median overall survival was 54.7 months. However, median progression-free survival and median overall survival varied significantly among the four assigned groups. It was 26.7 months for group 1, 20.7 months for group 2, 16.2 months for group 3, and 13.6 months for group 4 (P less than .001). At the same time, median overall survival was 83.4 months for group 1, 54.5 months for 2, 43.8 months for group 3, and 38.9 months for group 4 (P less than .001).

To be consistent with the vast majority of the existing literature, which used the cut-off of 10 mm to define optimal residual disease, Dr. Sioulas and his associates merged patients with residual disease 1-5 mm and 6-10 mm into one group and found that its median overall survival was 52.6 months. Patients with residual disease of 1-10 mm had significantly better overall survival, as compared to those with residual disease greater than 10 mm (P less than .001). Importantly, among the patients with residual disease of 1-10 mm, the administration of at least one cycle of primary intraperitoneal chemotherapy was associated with significantly prolonged overall survival, as compared to the sole use of intravenous chemotherapy. The median overall survival for those groups was 65.1 and 40.6 months, respectively (P = .002).

“I certainly believe neoadjuvant chemotherapy is the best approach in certain situations, but I don’t think it should be the knee-jerk reflex for all patients with advanced ovarian cancer,” Dr. Chi said. “I think that may be doing a disservice to many patients who could get a distinct prolongation of life and overall survival, or even cure, with a primary debulking surgery approach.”

He noted that ovarian cancer “goes where it wants to go. It doesn’t care what the training or surgical capabilities of the surgeon are. It’s going to go where it wants to go, so you can’t make the patient and the disease fit into your training skill set. You have to adapt your training skill set to the disease.”

The ideal study of this issue, Dr. Chi said, would “compare 400 or 500 patients with primary debulking and 400 or 500 patients who receive neoadjuvant chemotherapy to see which approach is better. There are two trials that have been done in Europe and have shown that it doesn’t matter, that the outcomes are the same whether you do primary debulking first or neoadjuvant chemotherapy first [see N. Engl. J. Med. 2010;363;943-53 and Lancet 2015;386:249-57]. Unfortunately, the survival outcomes in their primary debulking surgery arm were much lower as compared to other studies, especially those conducted in the United States. This highlights the importance of homogeneity in advanced surgical skills as a prerequisite before we draw definite conclusions about the survival outcomes after primary debulking surgery in patients with advanced disease.”

Dr. Chi acknowledged certain limitations of the study, including its retrospective design and the fact that surgeons at Memorial Sloan Kettering “are more willing, and have more support staff available, to perform comprehensive surgeries than at other centers.”

[email protected]

SAN DIEGO – There is a survival benefit to debulking stage IIIC ovarian, fallopian tube, and peritoneal tumors down to 10mm or smaller in size, a single-center retrospective study demonstrated.

“You shouldn’t just relegate those patients [in whom] you can’t get a complete gross resection to neoadjuvant chemotherapy, because their median survival is going to generally be around 30-36 months,” Dr. Dennis S. Chi said in an interview in advance of the annual meeting of Society of Gynecologic Oncology. “But if you do a primary debulking and you get the volume of residual disease down to 10 mm or smaller in maximal diameter, the median survivals can be in the mid-40s to over 80 months.”

Dr. Chi, head of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center, New York, said that the current findings come at a time when the initial management of advanced ovarian cancer is in flux and is controversial. “For decades it used to be that the initial step was to do an operation and to do a primary debulking surgery,” he said. “But studies in the 1980s and 1990s showed that if you did primary debulking surgery and you did the standard surgery that gynecologic oncologists did at that time, greater than 50% of the time you would not do an operation that would result in an optimal debulking, where you get all or almost all of the visible cancer out.”

Two camps formed, he continued, one consisting of clinicians who believe “we need to do better surgery, or more comprehensive surgery,” and another group of clinicians who say, “Why don’t we treat with chemotherapy first for three treatments, and then do surgery? Maybe this will shrink the cancer and consequently improve the surgical outcome.’ Both camps agree that if you cannot get all the cancer out or almost all the cancer out, then you should start with chemotherapy first. The question then lies, what is the cut-off?”

In a study led by Dr. Chi and Dr. Vasileios Sioulas, the Senior International Gynecologic Oncology Fellow at Memorial Sloan Kettering Cancer Center, the authors set out to explore the effect of primary cytoreduction to minimal but gross residual disease in women with bulky stage IIIC ovarian/fallopian tube/primary peritoneal cancer. They retrospectively evaluated the records of 496 women who underwent primary debulking surgery at the cancer center between 2001 and 2010. Their median age was 62 years, the median operative time was 265 minutes, and 46% of the patients received at least one cycle of primary or consolidation intraperitoneal chemotherapy.

The researchers assigned patients to one of four groups based on reported gross residual disease. More than one-third (37%) had no gross residual disease (group 1); 26% had residual disease of 1-5 mm in diameter (group 2); 11% had residual disease of 6-10 mm in diameter (group 3), and 26% had residual disease that exceeded 10 mm in diameter (group 4). The median follow-up in the entire cohort was 53 months, the median progression-free survival was 18.6 months, and the median overall survival was 54.7 months. However, median progression-free survival and median overall survival varied significantly among the four assigned groups. It was 26.7 months for group 1, 20.7 months for group 2, 16.2 months for group 3, and 13.6 months for group 4 (P less than .001). At the same time, median overall survival was 83.4 months for group 1, 54.5 months for 2, 43.8 months for group 3, and 38.9 months for group 4 (P less than .001).

To be consistent with the vast majority of the existing literature, which used the cut-off of 10 mm to define optimal residual disease, Dr. Sioulas and his associates merged patients with residual disease 1-5 mm and 6-10 mm into one group and found that its median overall survival was 52.6 months. Patients with residual disease of 1-10 mm had significantly better overall survival, as compared to those with residual disease greater than 10 mm (P less than .001). Importantly, among the patients with residual disease of 1-10 mm, the administration of at least one cycle of primary intraperitoneal chemotherapy was associated with significantly prolonged overall survival, as compared to the sole use of intravenous chemotherapy. The median overall survival for those groups was 65.1 and 40.6 months, respectively (P = .002).

“I certainly believe neoadjuvant chemotherapy is the best approach in certain situations, but I don’t think it should be the knee-jerk reflex for all patients with advanced ovarian cancer,” Dr. Chi said. “I think that may be doing a disservice to many patients who could get a distinct prolongation of life and overall survival, or even cure, with a primary debulking surgery approach.”

He noted that ovarian cancer “goes where it wants to go. It doesn’t care what the training or surgical capabilities of the surgeon are. It’s going to go where it wants to go, so you can’t make the patient and the disease fit into your training skill set. You have to adapt your training skill set to the disease.”

The ideal study of this issue, Dr. Chi said, would “compare 400 or 500 patients with primary debulking and 400 or 500 patients who receive neoadjuvant chemotherapy to see which approach is better. There are two trials that have been done in Europe and have shown that it doesn’t matter, that the outcomes are the same whether you do primary debulking first or neoadjuvant chemotherapy first [see N. Engl. J. Med. 2010;363;943-53 and Lancet 2015;386:249-57]. Unfortunately, the survival outcomes in their primary debulking surgery arm were much lower as compared to other studies, especially those conducted in the United States. This highlights the importance of homogeneity in advanced surgical skills as a prerequisite before we draw definite conclusions about the survival outcomes after primary debulking surgery in patients with advanced disease.”

Dr. Chi acknowledged certain limitations of the study, including its retrospective design and the fact that surgeons at Memorial Sloan Kettering “are more willing, and have more support staff available, to perform comprehensive surgeries than at other centers.”

[email protected]

SAN DIEGO – Women with advanced ovarian cancer who possess a mutation in a homologous recombination DNA repair gene have impressively longer progression-free and overall survival in response to therapy than those who don’t, Dr. Barbara S. Norquist reported at the annual meeting of the Society of Gynecologic Oncology.

What’s more, these mutations are common in women with ovarian cancer. Of 1,195 patients with advanced ovarian cancer enrolled in the phase III Gynecology Oncology Group 218 trial, fully 25.7% – or 1 in 4 patients – had a mutation in BRCA1, BRCA2, or one of 14 other homologous recombination DNA repair genes included in the BROCA-HR gene panel test, according to Dr. Norquist, a gynecologic oncologist at the University of Washington, Seattle.

Defects in these genes were associated with improved survival in GOG 218. The most impressive gain in overall survival was seen in women with a BRCA2 mutation: their median overall survival was 33.1 months longer than in patients with no mutations.

In a multivariate analysis adjusted for treatment, stage, residual disease, and performance status, the likelihood of disease progression was reduced by 20% in patients with a BRCA1 mutation compared to women with no mutations, by 48% in patients with a BRCA2 mutation, and by 27% in those with non-BRCA HR mutations. The risk of death was reduced by 26% in patients with a BRCA1 mutation, by 64% in those with a BRCA2 mutation, and by 33% in those with other HR mutations, according to Dr. Norquist.

Mutation status proved unrelated to patient age, histologic tumor type, or family history. That’s a key finding, she stressed. The clinical implication is that all women with any type of ovarian cancer should undergo genetic testing for mutations in homologous recombination genes.

Forty-eight percent of women in the homologous recombination (HR) gene mutation-positive cohort had a damaging mutation in BRCA1, 25% in BRCA2, and 27% in one of the 14 other HR genes included in the BROCA-HR gene test panel. The BROCA-HR gene test panel was developed by University of Washington physicians and is commercially available through the university’s department of laboratory medicine. Dr. Norquist noted, however, that these 16 genes are included in most gene panel tests.

Testing only for BRCA1/2 mutations, while less expensive than testing for the full set of 16 HR genes, would have missed 27% of patients who had one of the other mutations linked to improved prognosis, she observed.

The GOG 218 study was a randomized, placebo-controlled trial designed to evaluate the impact of adding extended bevacizumab to first-line chemotherapy for advanced ovarian cancer. The main finding was that bevacizumab modestly improved progression-free survival by about 3 months (N Engl J Med. 2011 Dec 29;365(26):2473-83). Dr. Norquist’s secondary analysis of the GOG 218 dataset looked at whether HR mutation status could be used to identify a patient subset who would get a more robust benefit from bevacizumab; it did not.

“How I would interpret this clinically is that if a clinician feels their patient is a candidate for bevacizumab, we don’t have sufficient evidence at this time that mutation status should impact that decision,” she said.

Dr. Norquist was honored with the Society of Gynecologic Oncology annual President’s Award, bestowed for the study presented at the meeting which is judged to have the biggest direct effect on the care of women with gynecologic cancer.

Discussant Dr. Kristin Zorn was strongly supportive of the award going to Dr. Norquist.

“I think what this amounts to is a change in the standard of care for ovarian cancer. If you care for ovarian cancer patients, it’s imperative to have adequate training to provide genetic counseling and testing, or to know how to refer to appropriate genetic professionals in your practice setting,” according to Dr. Zorn of the University of Arkansas for Medical Sciences in Little Rock.

She endorsed Dr. Norquist’s call for genetic screening for HR deficiency in all patients with ovarian, fallopian tube, or primary peritoneal cancer regardless of tumor histology, family history of cancer, or ethnicity. Dr. Zorn noted that stance has been an underappreciated element in National Comprehensive Cancer Network guidelines since 2011.

“That knowledge of HR mutation status has such an impact for that patient and her family,” Dr. Zorn stressed.

Based upon other evidence, she added, it’s quite possible that the true proportion of ovarian cancer patients with HR deficiency could be as high as 50%, rather than the 26% figure Dr. Norquist reported in her GOG 218 analysis. That’s because for many participants in GOG 218, DNA was available from either germline or somatic samples, but not both.

The new understanding of the importance of HR deficiency has important implications for the design of clinical trials. At present many trials of potential new treatments for ovarian cancer restrict enrollment to patients with high-grade serous disease. It’s now clear that such restrictions exclude many patients who could benefit from drugs with activity in the setting of HR deficiency, Dr. Zorn said.

Homologous recombination deficiency increases tumor sensitivity to a variety of medications, including platinum, pegylated liposomal doxorubicin, antiangiogenic agents, and PARP inhibitors, she added.

The 16 HR genes Dr. Norquist scrutinized in GOG 218 are BRCA1/2, BRIP1, PALB2, RAD51C, RAD51D, ATM, ATR, NBN, SLX4, BARD1, BLM, CHEK2, RBBP8, MRE11A, and XRCC2. These genes lie along what has come to be called the Fanconi Anemia/BRCA homologous recombination pathway.

[email protected]

SAN DIEGO – Women with advanced ovarian cancer who possess a mutation in a homologous recombination DNA repair gene have impressively longer progression-free and overall survival in response to therapy than those who don’t, Dr. Barbara S. Norquist reported at the annual meeting of the Society of Gynecologic Oncology.

What’s more, these mutations are common in women with ovarian cancer. Of 1,195 patients with advanced ovarian cancer enrolled in the phase III Gynecology Oncology Group 218 trial, fully 25.7% – or 1 in 4 patients – had a mutation in BRCA1, BRCA2, or one of 14 other homologous recombination DNA repair genes included in the BROCA-HR gene panel test, according to Dr. Norquist, a gynecologic oncologist at the University of Washington, Seattle.

Defects in these genes were associated with improved survival in GOG 218. The most impressive gain in overall survival was seen in women with a BRCA2 mutation: their median overall survival was 33.1 months longer than in patients with no mutations.

In a multivariate analysis adjusted for treatment, stage, residual disease, and performance status, the likelihood of disease progression was reduced by 20% in patients with a BRCA1 mutation compared to women with no mutations, by 48% in patients with a BRCA2 mutation, and by 27% in those with non-BRCA HR mutations. The risk of death was reduced by 26% in patients with a BRCA1 mutation, by 64% in those with a BRCA2 mutation, and by 33% in those with other HR mutations, according to Dr. Norquist.

Mutation status proved unrelated to patient age, histologic tumor type, or family history. That’s a key finding, she stressed. The clinical implication is that all women with any type of ovarian cancer should undergo genetic testing for mutations in homologous recombination genes.

Forty-eight percent of women in the homologous recombination (HR) gene mutation-positive cohort had a damaging mutation in BRCA1, 25% in BRCA2, and 27% in one of the 14 other HR genes included in the BROCA-HR gene test panel. The BROCA-HR gene test panel was developed by University of Washington physicians and is commercially available through the university’s department of laboratory medicine. Dr. Norquist noted, however, that these 16 genes are included in most gene panel tests.

Testing only for BRCA1/2 mutations, while less expensive than testing for the full set of 16 HR genes, would have missed 27% of patients who had one of the other mutations linked to improved prognosis, she observed.

The GOG 218 study was a randomized, placebo-controlled trial designed to evaluate the impact of adding extended bevacizumab to first-line chemotherapy for advanced ovarian cancer. The main finding was that bevacizumab modestly improved progression-free survival by about 3 months (N Engl J Med. 2011 Dec 29;365(26):2473-83). Dr. Norquist’s secondary analysis of the GOG 218 dataset looked at whether HR mutation status could be used to identify a patient subset who would get a more robust benefit from bevacizumab; it did not.

“How I would interpret this clinically is that if a clinician feels their patient is a candidate for bevacizumab, we don’t have sufficient evidence at this time that mutation status should impact that decision,” she said.

Dr. Norquist was honored with the Society of Gynecologic Oncology annual President’s Award, bestowed for the study presented at the meeting which is judged to have the biggest direct effect on the care of women with gynecologic cancer.

Discussant Dr. Kristin Zorn was strongly supportive of the award going to Dr. Norquist.

“I think what this amounts to is a change in the standard of care for ovarian cancer. If you care for ovarian cancer patients, it’s imperative to have adequate training to provide genetic counseling and testing, or to know how to refer to appropriate genetic professionals in your practice setting,” according to Dr. Zorn of the University of Arkansas for Medical Sciences in Little Rock.

She endorsed Dr. Norquist’s call for genetic screening for HR deficiency in all patients with ovarian, fallopian tube, or primary peritoneal cancer regardless of tumor histology, family history of cancer, or ethnicity. Dr. Zorn noted that stance has been an underappreciated element in National Comprehensive Cancer Network guidelines since 2011.

“That knowledge of HR mutation status has such an impact for that patient and her family,” Dr. Zorn stressed.

Based upon other evidence, she added, it’s quite possible that the true proportion of ovarian cancer patients with HR deficiency could be as high as 50%, rather than the 26% figure Dr. Norquist reported in her GOG 218 analysis. That’s because for many participants in GOG 218, DNA was available from either germline or somatic samples, but not both.

The new understanding of the importance of HR deficiency has important implications for the design of clinical trials. At present many trials of potential new treatments for ovarian cancer restrict enrollment to patients with high-grade serous disease. It’s now clear that such restrictions exclude many patients who could benefit from drugs with activity in the setting of HR deficiency, Dr. Zorn said.

Homologous recombination deficiency increases tumor sensitivity to a variety of medications, including platinum, pegylated liposomal doxorubicin, antiangiogenic agents, and PARP inhibitors, she added.

The 16 HR genes Dr. Norquist scrutinized in GOG 218 are BRCA1/2, BRIP1, PALB2, RAD51C, RAD51D, ATM, ATR, NBN, SLX4, BARD1, BLM, CHEK2, RBBP8, MRE11A, and XRCC2. These genes lie along what has come to be called the Fanconi Anemia/BRCA homologous recombination pathway.

[email protected]

SAN DIEGO – Women with advanced ovarian cancer who possess a mutation in a homologous recombination DNA repair gene have impressively longer progression-free and overall survival in response to therapy than those who don’t, Dr. Barbara S. Norquist reported at the annual meeting of the Society of Gynecologic Oncology.

What’s more, these mutations are common in women with ovarian cancer. Of 1,195 patients with advanced ovarian cancer enrolled in the phase III Gynecology Oncology Group 218 trial, fully 25.7% – or 1 in 4 patients – had a mutation in BRCA1, BRCA2, or one of 14 other homologous recombination DNA repair genes included in the BROCA-HR gene panel test, according to Dr. Norquist, a gynecologic oncologist at the University of Washington, Seattle.

Defects in these genes were associated with improved survival in GOG 218. The most impressive gain in overall survival was seen in women with a BRCA2 mutation: their median overall survival was 33.1 months longer than in patients with no mutations.

In a multivariate analysis adjusted for treatment, stage, residual disease, and performance status, the likelihood of disease progression was reduced by 20% in patients with a BRCA1 mutation compared to women with no mutations, by 48% in patients with a BRCA2 mutation, and by 27% in those with non-BRCA HR mutations. The risk of death was reduced by 26% in patients with a BRCA1 mutation, by 64% in those with a BRCA2 mutation, and by 33% in those with other HR mutations, according to Dr. Norquist.

Mutation status proved unrelated to patient age, histologic tumor type, or family history. That’s a key finding, she stressed. The clinical implication is that all women with any type of ovarian cancer should undergo genetic testing for mutations in homologous recombination genes.

Forty-eight percent of women in the homologous recombination (HR) gene mutation-positive cohort had a damaging mutation in BRCA1, 25% in BRCA2, and 27% in one of the 14 other HR genes included in the BROCA-HR gene test panel. The BROCA-HR gene test panel was developed by University of Washington physicians and is commercially available through the university’s department of laboratory medicine. Dr. Norquist noted, however, that these 16 genes are included in most gene panel tests.

Testing only for BRCA1/2 mutations, while less expensive than testing for the full set of 16 HR genes, would have missed 27% of patients who had one of the other mutations linked to improved prognosis, she observed.

The GOG 218 study was a randomized, placebo-controlled trial designed to evaluate the impact of adding extended bevacizumab to first-line chemotherapy for advanced ovarian cancer. The main finding was that bevacizumab modestly improved progression-free survival by about 3 months (N Engl J Med. 2011 Dec 29;365(26):2473-83). Dr. Norquist’s secondary analysis of the GOG 218 dataset looked at whether HR mutation status could be used to identify a patient subset who would get a more robust benefit from bevacizumab; it did not.

“How I would interpret this clinically is that if a clinician feels their patient is a candidate for bevacizumab, we don’t have sufficient evidence at this time that mutation status should impact that decision,” she said.

Dr. Norquist was honored with the Society of Gynecologic Oncology annual President’s Award, bestowed for the study presented at the meeting which is judged to have the biggest direct effect on the care of women with gynecologic cancer.

Discussant Dr. Kristin Zorn was strongly supportive of the award going to Dr. Norquist.

“I think what this amounts to is a change in the standard of care for ovarian cancer. If you care for ovarian cancer patients, it’s imperative to have adequate training to provide genetic counseling and testing, or to know how to refer to appropriate genetic professionals in your practice setting,” according to Dr. Zorn of the University of Arkansas for Medical Sciences in Little Rock.

She endorsed Dr. Norquist’s call for genetic screening for HR deficiency in all patients with ovarian, fallopian tube, or primary peritoneal cancer regardless of tumor histology, family history of cancer, or ethnicity. Dr. Zorn noted that stance has been an underappreciated element in National Comprehensive Cancer Network guidelines since 2011.

“That knowledge of HR mutation status has such an impact for that patient and her family,” Dr. Zorn stressed.

Based upon other evidence, she added, it’s quite possible that the true proportion of ovarian cancer patients with HR deficiency could be as high as 50%, rather than the 26% figure Dr. Norquist reported in her GOG 218 analysis. That’s because for many participants in GOG 218, DNA was available from either germline or somatic samples, but not both.

The new understanding of the importance of HR deficiency has important implications for the design of clinical trials. At present many trials of potential new treatments for ovarian cancer restrict enrollment to patients with high-grade serous disease. It’s now clear that such restrictions exclude many patients who could benefit from drugs with activity in the setting of HR deficiency, Dr. Zorn said.

Homologous recombination deficiency increases tumor sensitivity to a variety of medications, including platinum, pegylated liposomal doxorubicin, antiangiogenic agents, and PARP inhibitors, she added.

The 16 HR genes Dr. Norquist scrutinized in GOG 218 are BRCA1/2, BRIP1, PALB2, RAD51C, RAD51D, ATM, ATR, NBN, SLX4, BARD1, BLM, CHEK2, RBBP8, MRE11A, and XRCC2. These genes lie along what has come to be called the Fanconi Anemia/BRCA homologous recombination pathway.

[email protected]

SAN DIEGO – Following chemotherapy and surgery for gynecologic cancer, circulating tumor DNA identified recurrence in six of 32 women a mean of 7 months before it was detected on CT scan, Dr. John Martignetti reported at the annual meeting of the Society of Gynecologic Oncology. “The CT scan did not pick up cancer that ctDNA [circulating tumor DNA] did.” Meanwhile, while essentially every patient had detectable ctDNA when tumor was present on CT, only about 60% had elevated cancer antigen 125 (CA-125) levels, said Dr. Martignetti of the Icahn School of Medicine at Mount Sinai, New York.

In a subgroup of 10 patients with known survival outcomes, five with no ctDNA after primary treatment had 22-33 months progression free survival, and all were alive at up to 5.4 years follow-up. Four of the five with ctDNA after primary treatment died within 29 months; the other patient progressed immediately and was alive with disease at 4.8 years.

“We demonstrated for the first time that personalized ctDNA biomarkers in gynecologic cancers can detect the presence of residual tumor earlier than currently used serum and imaging studies and are an independent predictor of survival. [They] dynamically predict treatment response and survival in gynecologic cancers. The measurement of ctDNA in blood – dubbed liquid biopsy – is “a powerful emerging technology capable of providing accurate assessment of both tumor behavior and disease burden,” Dr. Martignetti said.

“These mutations are only made in cancer cells,” so if they are in the blood, there must be cancer somewhere, he said.

The Sinai team identified specific mutations – in, for example, P53 tumor suppression, beta-catenin, or BRAF genes – in tumor cells from 36 of 44 women, using targeted sequencing for likely mutations in 28 samples and whole exome sequencing in eight. Blood samples were checked for ctDNA in 32 women by droplet digital PCR; ctDNA was detected in 30 (94%). The patients had high-grade endometrial carcinomas or high-grade serous carcinomas of the ovary, fallopian tube, or peritoneum.

For six women, ctDNA detected recurrence 1-11 months before CT. In once case, CA-125 was within normal limits a month before bowel resection for recurrence, and a PET scan 3 months before was negative. “Seven months before her surgery, we could detect ctDNA,” Dr. Martignetti said. For the rest of the women, sensitivity and specificity correlated with CA-125 and CT.

Mount Sinai has been working on ctDNA for almost a decade, and is among the pioneers in the field. Every gynecologic cancer patient there has tumor samples collected for sequencing and blood samples for ctDNA testing.

With ctDNA, “you can monitor the evolution of tumor growth, response to treatment, acquired resistance, and development of tumor heterogeneity.” If there’s no ctDNA, it seems likely “that patients can go home and say ‘whew.’ Lingering mutations” suggest the need for closer follow-up and perhaps additional chemotherapy.

The ultimate goal of liquid biopsy is to tailor cancer treatment to specific tumor mutations. Patients with fibroblast growth factor receptor (FGFR) gene mutations could get an FGFR inhibitor; ovarian tumors with lung cancer mutations might get lung cancer drugs. The approach is being tested by the National Institutes of Health through the NCI-MATCH trial.

It seems likely there’s also a role in screening. The Sinai team detected tumor DNA mutations in the uterine lavage fluid of a woman who presented with postmenopausal bleeding. A week later, pathology identified a microscopic stage 1, grade 1 endometrial cancer in situ. “That’s the future,” Dr. Martignetti said.

[email protected]

SAN DIEGO – Following chemotherapy and surgery for gynecologic cancer, circulating tumor DNA identified recurrence in six of 32 women a mean of 7 months before it was detected on CT scan, Dr. John Martignetti reported at the annual meeting of the Society of Gynecologic Oncology. “The CT scan did not pick up cancer that ctDNA [circulating tumor DNA] did.” Meanwhile, while essentially every patient had detectable ctDNA when tumor was present on CT, only about 60% had elevated cancer antigen 125 (CA-125) levels, said Dr. Martignetti of the Icahn School of Medicine at Mount Sinai, New York.

In a subgroup of 10 patients with known survival outcomes, five with no ctDNA after primary treatment had 22-33 months progression free survival, and all were alive at up to 5.4 years follow-up. Four of the five with ctDNA after primary treatment died within 29 months; the other patient progressed immediately and was alive with disease at 4.8 years.

“We demonstrated for the first time that personalized ctDNA biomarkers in gynecologic cancers can detect the presence of residual tumor earlier than currently used serum and imaging studies and are an independent predictor of survival. [They] dynamically predict treatment response and survival in gynecologic cancers. The measurement of ctDNA in blood – dubbed liquid biopsy – is “a powerful emerging technology capable of providing accurate assessment of both tumor behavior and disease burden,” Dr. Martignetti said.

“These mutations are only made in cancer cells,” so if they are in the blood, there must be cancer somewhere, he said.

The Sinai team identified specific mutations – in, for example, P53 tumor suppression, beta-catenin, or BRAF genes – in tumor cells from 36 of 44 women, using targeted sequencing for likely mutations in 28 samples and whole exome sequencing in eight. Blood samples were checked for ctDNA in 32 women by droplet digital PCR; ctDNA was detected in 30 (94%). The patients had high-grade endometrial carcinomas or high-grade serous carcinomas of the ovary, fallopian tube, or peritoneum.

For six women, ctDNA detected recurrence 1-11 months before CT. In once case, CA-125 was within normal limits a month before bowel resection for recurrence, and a PET scan 3 months before was negative. “Seven months before her surgery, we could detect ctDNA,” Dr. Martignetti said. For the rest of the women, sensitivity and specificity correlated with CA-125 and CT.

Mount Sinai has been working on ctDNA for almost a decade, and is among the pioneers in the field. Every gynecologic cancer patient there has tumor samples collected for sequencing and blood samples for ctDNA testing.

With ctDNA, “you can monitor the evolution of tumor growth, response to treatment, acquired resistance, and development of tumor heterogeneity.” If there’s no ctDNA, it seems likely “that patients can go home and say ‘whew.’ Lingering mutations” suggest the need for closer follow-up and perhaps additional chemotherapy.

The ultimate goal of liquid biopsy is to tailor cancer treatment to specific tumor mutations. Patients with fibroblast growth factor receptor (FGFR) gene mutations could get an FGFR inhibitor; ovarian tumors with lung cancer mutations might get lung cancer drugs. The approach is being tested by the National Institutes of Health through the NCI-MATCH trial.

It seems likely there’s also a role in screening. The Sinai team detected tumor DNA mutations in the uterine lavage fluid of a woman who presented with postmenopausal bleeding. A week later, pathology identified a microscopic stage 1, grade 1 endometrial cancer in situ. “That’s the future,” Dr. Martignetti said.

[email protected]

SAN DIEGO – Following chemotherapy and surgery for gynecologic cancer, circulating tumor DNA identified recurrence in six of 32 women a mean of 7 months before it was detected on CT scan, Dr. John Martignetti reported at the annual meeting of the Society of Gynecologic Oncology. “The CT scan did not pick up cancer that ctDNA [circulating tumor DNA] did.” Meanwhile, while essentially every patient had detectable ctDNA when tumor was present on CT, only about 60% had elevated cancer antigen 125 (CA-125) levels, said Dr. Martignetti of the Icahn School of Medicine at Mount Sinai, New York.

In a subgroup of 10 patients with known survival outcomes, five with no ctDNA after primary treatment had 22-33 months progression free survival, and all were alive at up to 5.4 years follow-up. Four of the five with ctDNA after primary treatment died within 29 months; the other patient progressed immediately and was alive with disease at 4.8 years.

“We demonstrated for the first time that personalized ctDNA biomarkers in gynecologic cancers can detect the presence of residual tumor earlier than currently used serum and imaging studies and are an independent predictor of survival. [They] dynamically predict treatment response and survival in gynecologic cancers. The measurement of ctDNA in blood – dubbed liquid biopsy – is “a powerful emerging technology capable of providing accurate assessment of both tumor behavior and disease burden,” Dr. Martignetti said.

“These mutations are only made in cancer cells,” so if they are in the blood, there must be cancer somewhere, he said.

The Sinai team identified specific mutations – in, for example, P53 tumor suppression, beta-catenin, or BRAF genes – in tumor cells from 36 of 44 women, using targeted sequencing for likely mutations in 28 samples and whole exome sequencing in eight. Blood samples were checked for ctDNA in 32 women by droplet digital PCR; ctDNA was detected in 30 (94%). The patients had high-grade endometrial carcinomas or high-grade serous carcinomas of the ovary, fallopian tube, or peritoneum.

For six women, ctDNA detected recurrence 1-11 months before CT. In once case, CA-125 was within normal limits a month before bowel resection for recurrence, and a PET scan 3 months before was negative. “Seven months before her surgery, we could detect ctDNA,” Dr. Martignetti said. For the rest of the women, sensitivity and specificity correlated with CA-125 and CT.

Mount Sinai has been working on ctDNA for almost a decade, and is among the pioneers in the field. Every gynecologic cancer patient there has tumor samples collected for sequencing and blood samples for ctDNA testing.

With ctDNA, “you can monitor the evolution of tumor growth, response to treatment, acquired resistance, and development of tumor heterogeneity.” If there’s no ctDNA, it seems likely “that patients can go home and say ‘whew.’ Lingering mutations” suggest the need for closer follow-up and perhaps additional chemotherapy.

The ultimate goal of liquid biopsy is to tailor cancer treatment to specific tumor mutations. Patients with fibroblast growth factor receptor (FGFR) gene mutations could get an FGFR inhibitor; ovarian tumors with lung cancer mutations might get lung cancer drugs. The approach is being tested by the National Institutes of Health through the NCI-MATCH trial.

It seems likely there’s also a role in screening. The Sinai team detected tumor DNA mutations in the uterine lavage fluid of a woman who presented with postmenopausal bleeding. A week later, pathology identified a microscopic stage 1, grade 1 endometrial cancer in situ. “That’s the future,” Dr. Martignetti said.

[email protected]

SAN DIEGO – A novel dual AKT and P70S6K inhibitor decreased tumor growth metastases in multiple animal models of ovarian and uterine cancer, results from a novel study demonstrated. It also prolonged survival and led to regression and stabilization of tumor growth in uterine cancer mouse models.

MSC2363318A, an investigational agent being developed by EMD Serono, is a novel inhibitor of AKT1, AKT3, and P70S6K, Dr. Rebecca A. Previs said in an interview in advance of the annual meeting of Society of Gynecologic Oncology, where she would be presenting the study results. “Due to the high rate of dysregulation of the PI3K/AKT/P70S6K pathway in ovarian and uterine malignancies, we tested this compound in multiple animal models of ovarian and uterine cancer,” she said. “Dual AKT/P70S6K inhibition provides a novel therapeutic approach by promoting improved PI3K/AKT pathway inhibition while avoiding the negative effects of AKT activation through compensatory feedback loops, including IRS-1. Additionally, inhibition of two targets further downstream in a hyperactive pathway in solid malignancies could avoid the side effects seen with historical pan-PI3K inhibitors. The present investigation is the first report of this novel compound.”

Dr. Previs, of the University of Texas MD Anderson Cancer Center, Houston, and her , used orthotopic murine models of ovarian and uterine cancer, and MTT, Western blot analysis, and plasmid transfection to determine the biological and mechanistic effects of MSC2363318A. High-throughput analyses were carried out to identify underlying mechanisms and biomarkers of response.

The researchers found that dual inhibition of AKT and P70S6K had therapeutic efficacy in multiple preclinical models by directly promoting apoptosis of tumor cells, halting proliferation, and reducing angiogenesis. They observed treatment synergy in both uterine and ovarian cancer types with the combination of MSC2363318A and paclitaxel, a commonly used chemotherapy drug (P less than .001). High-throughput analyses identified YAP1 as a candidate biomarker to predict cell lines that were most sensitive to MSC2363318A (P = .0015).

“Our investigation supports further clinical development of MSC2363318A in ovarian and uterine cancer patients,” Dr. Previs said. “This compound could be used in combination with paclitaxel in the frontline setting or to restore sensitivity to anti-angiogenic therapies like bevacizumab in the setting of recurrent disease.”

She acknowledged certain limitations of the study, including the fact that it used preclinical models of ovarian and uterine cancer. “Clinical proof of activity is pending upcoming trials,” she said.

Dr. Previs reported that EMD Serono provided the study drug and provided partial research support.

[email protected]

SAN DIEGO – A novel dual AKT and P70S6K inhibitor decreased tumor growth metastases in multiple animal models of ovarian and uterine cancer, results from a novel study demonstrated. It also prolonged survival and led to regression and stabilization of tumor growth in uterine cancer mouse models.

MSC2363318A, an investigational agent being developed by EMD Serono, is a novel inhibitor of AKT1, AKT3, and P70S6K, Dr. Rebecca A. Previs said in an interview in advance of the annual meeting of Society of Gynecologic Oncology, where she would be presenting the study results. “Due to the high rate of dysregulation of the PI3K/AKT/P70S6K pathway in ovarian and uterine malignancies, we tested this compound in multiple animal models of ovarian and uterine cancer,” she said. “Dual AKT/P70S6K inhibition provides a novel therapeutic approach by promoting improved PI3K/AKT pathway inhibition while avoiding the negative effects of AKT activation through compensatory feedback loops, including IRS-1. Additionally, inhibition of two targets further downstream in a hyperactive pathway in solid malignancies could avoid the side effects seen with historical pan-PI3K inhibitors. The present investigation is the first report of this novel compound.”

Dr. Previs, of the University of Texas MD Anderson Cancer Center, Houston, and her , used orthotopic murine models of ovarian and uterine cancer, and MTT, Western blot analysis, and plasmid transfection to determine the biological and mechanistic effects of MSC2363318A. High-throughput analyses were carried out to identify underlying mechanisms and biomarkers of response.

The researchers found that dual inhibition of AKT and P70S6K had therapeutic efficacy in multiple preclinical models by directly promoting apoptosis of tumor cells, halting proliferation, and reducing angiogenesis. They observed treatment synergy in both uterine and ovarian cancer types with the combination of MSC2363318A and paclitaxel, a commonly used chemotherapy drug (P less than .001). High-throughput analyses identified YAP1 as a candidate biomarker to predict cell lines that were most sensitive to MSC2363318A (P = .0015).

“Our investigation supports further clinical development of MSC2363318A in ovarian and uterine cancer patients,” Dr. Previs said. “This compound could be used in combination with paclitaxel in the frontline setting or to restore sensitivity to anti-angiogenic therapies like bevacizumab in the setting of recurrent disease.”

She acknowledged certain limitations of the study, including the fact that it used preclinical models of ovarian and uterine cancer. “Clinical proof of activity is pending upcoming trials,” she said.

Dr. Previs reported that EMD Serono provided the study drug and provided partial research support.

[email protected]

SAN DIEGO – A novel dual AKT and P70S6K inhibitor decreased tumor growth metastases in multiple animal models of ovarian and uterine cancer, results from a novel study demonstrated. It also prolonged survival and led to regression and stabilization of tumor growth in uterine cancer mouse models.

MSC2363318A, an investigational agent being developed by EMD Serono, is a novel inhibitor of AKT1, AKT3, and P70S6K, Dr. Rebecca A. Previs said in an interview in advance of the annual meeting of Society of Gynecologic Oncology, where she would be presenting the study results. “Due to the high rate of dysregulation of the PI3K/AKT/P70S6K pathway in ovarian and uterine malignancies, we tested this compound in multiple animal models of ovarian and uterine cancer,” she said. “Dual AKT/P70S6K inhibition provides a novel therapeutic approach by promoting improved PI3K/AKT pathway inhibition while avoiding the negative effects of AKT activation through compensatory feedback loops, including IRS-1. Additionally, inhibition of two targets further downstream in a hyperactive pathway in solid malignancies could avoid the side effects seen with historical pan-PI3K inhibitors. The present investigation is the first report of this novel compound.”

Dr. Previs, of the University of Texas MD Anderson Cancer Center, Houston, and her , used orthotopic murine models of ovarian and uterine cancer, and MTT, Western blot analysis, and plasmid transfection to determine the biological and mechanistic effects of MSC2363318A. High-throughput analyses were carried out to identify underlying mechanisms and biomarkers of response.

The researchers found that dual inhibition of AKT and P70S6K had therapeutic efficacy in multiple preclinical models by directly promoting apoptosis of tumor cells, halting proliferation, and reducing angiogenesis. They observed treatment synergy in both uterine and ovarian cancer types with the combination of MSC2363318A and paclitaxel, a commonly used chemotherapy drug (P less than .001). High-throughput analyses identified YAP1 as a candidate biomarker to predict cell lines that were most sensitive to MSC2363318A (P = .0015).

“Our investigation supports further clinical development of MSC2363318A in ovarian and uterine cancer patients,” Dr. Previs said. “This compound could be used in combination with paclitaxel in the frontline setting or to restore sensitivity to anti-angiogenic therapies like bevacizumab in the setting of recurrent disease.”

She acknowledged certain limitations of the study, including the fact that it used preclinical models of ovarian and uterine cancer. “Clinical proof of activity is pending upcoming trials,” she said.

Dr. Previs reported that EMD Serono provided the study drug and provided partial research support.

[email protected]

Dr. Paola A. Gehrig picks presentations she anticipates to be the most interesting at the upcoming Society of Gynecologic Oncology annual meeting in San Diego.

1 – Mutations in homologous recombination genes and response to treatment in GOG 218: An NRG Oncology study

B.S. Norquista, et al.

Study objectives: Gynecologic Oncology Group (GOG) 218 was a phase III, randomized trial of advanced primary ovarian, fallopian tube, and peritoneal carcinoma, examining the role of adding bevacizumab to every-21-day carboplatin and paclitaxel. The objective was to examine whether mutations in homologous recombination genes affect response to treatment.

3 – Efficacy and safety of trabectedin or dacarbazine for the treatment of patients with uterine leiomyosarcoma after prior chemotherapy: A subgroup analysis of the randomized phase III SAR-3007 study

M.L. Hensleya, et al.

Study objectives: In ET743-SAR-3007, the efficacy of trabectedin in patients with advanced leiomyosarcoma (LMS) or liposarcoma (LPS), after chemotherapy failure, was compared with the active comparator dacarbazine. As reported, trabectedin exhibited improved disease control with median progression-free survival of 4.2 months (vs 1.5 months for dacarbazine) (HR 0.55; P less than .0001), with similar efficacy in both LMS and LPS cohorts. An analysis was conducted to assess the efficacy and safety of trabectedin or dacarbazine in the largest subgroup of the study, the 232 women with uterine LMS, who comprised 40.2% of the study participants.

10 – GOG 186H: A randomized phase II evaluation of weekly paclitaxel versus weekly paclitaxel with oncolytic reovirus in the treatment of recurrent or persistent ovarian, fallopian tube, or primary peritoneal cancer

D.E. Cohna, et al.

Study objectives: To assess whether the addition of oncolytic reovirus to weekly paclitaxel treatment prolonged progression-free survival in women with recurrent or persistent ovarian, tubal, or primary peritoneal cancer.

25 – Common single nucleotide polymorphisms associated with ovarian cancer risk contribute to the racial disparity in incidence

A. Berchucka, et al.

Study objectives: Data from the U.S. Surveillance, Epidemiology and End Results (SEER) registry have shown that ovarian cancer incidence is 35% lower in blacks than in whites. Differences in oophorectomy rates and epidemiologic risk factors such as parity and oral contraceptive use explain about 30% of this disparity. The Ovarian Cancer Association Consortium has identified 18 genome-wide significant common low-penetrance single nucleotide polymorphisms (SNPs) that increase ovarian cancer risk. Investigators examined whether these risk alleles are more common in whites than blacks to determine whether this contributes to the racial disparity in ovarian cancer incidence.

47 – A stratified randomized double-blind phase II trial of celecoxib in the treatment of patients with cervical intraepithelial neoplasia: A Gynecologic Oncology Group (GOG 0207) study with translational biomarkers and drug level monitoring

J.S. Radera, et al.

Study objectives: To examine the effect of celecoxib on cervical intraepithelial neoplasia type 3 based on whether or not the patient had regression of disease.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill.

Dr. Paola A. Gehrig picks presentations she anticipates to be the most interesting at the upcoming Society of Gynecologic Oncology annual meeting in San Diego.

1 – Mutations in homologous recombination genes and response to treatment in GOG 218: An NRG Oncology study

B.S. Norquista, et al.

Study objectives: Gynecologic Oncology Group (GOG) 218 was a phase III, randomized trial of advanced primary ovarian, fallopian tube, and peritoneal carcinoma, examining the role of adding bevacizumab to every-21-day carboplatin and paclitaxel. The objective was to examine whether mutations in homologous recombination genes affect response to treatment.

3 – Efficacy and safety of trabectedin or dacarbazine for the treatment of patients with uterine leiomyosarcoma after prior chemotherapy: A subgroup analysis of the randomized phase III SAR-3007 study

M.L. Hensleya, et al.

Study objectives: In ET743-SAR-3007, the efficacy of trabectedin in patients with advanced leiomyosarcoma (LMS) or liposarcoma (LPS), after chemotherapy failure, was compared with the active comparator dacarbazine. As reported, trabectedin exhibited improved disease control with median progression-free survival of 4.2 months (vs 1.5 months for dacarbazine) (HR 0.55; P less than .0001), with similar efficacy in both LMS and LPS cohorts. An analysis was conducted to assess the efficacy and safety of trabectedin or dacarbazine in the largest subgroup of the study, the 232 women with uterine LMS, who comprised 40.2% of the study participants.

10 – GOG 186H: A randomized phase II evaluation of weekly paclitaxel versus weekly paclitaxel with oncolytic reovirus in the treatment of recurrent or persistent ovarian, fallopian tube, or primary peritoneal cancer

D.E. Cohna, et al.

Study objectives: To assess whether the addition of oncolytic reovirus to weekly paclitaxel treatment prolonged progression-free survival in women with recurrent or persistent ovarian, tubal, or primary peritoneal cancer.

25 – Common single nucleotide polymorphisms associated with ovarian cancer risk contribute to the racial disparity in incidence

A. Berchucka, et al.

Study objectives: Data from the U.S. Surveillance, Epidemiology and End Results (SEER) registry have shown that ovarian cancer incidence is 35% lower in blacks than in whites. Differences in oophorectomy rates and epidemiologic risk factors such as parity and oral contraceptive use explain about 30% of this disparity. The Ovarian Cancer Association Consortium has identified 18 genome-wide significant common low-penetrance single nucleotide polymorphisms (SNPs) that increase ovarian cancer risk. Investigators examined whether these risk alleles are more common in whites than blacks to determine whether this contributes to the racial disparity in ovarian cancer incidence.

47 – A stratified randomized double-blind phase II trial of celecoxib in the treatment of patients with cervical intraepithelial neoplasia: A Gynecologic Oncology Group (GOG 0207) study with translational biomarkers and drug level monitoring

J.S. Radera, et al.

Study objectives: To examine the effect of celecoxib on cervical intraepithelial neoplasia type 3 based on whether or not the patient had regression of disease.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill.

Dr. Paola A. Gehrig picks presentations she anticipates to be the most interesting at the upcoming Society of Gynecologic Oncology annual meeting in San Diego.

1 – Mutations in homologous recombination genes and response to treatment in GOG 218: An NRG Oncology study

B.S. Norquista, et al.

Study objectives: Gynecologic Oncology Group (GOG) 218 was a phase III, randomized trial of advanced primary ovarian, fallopian tube, and peritoneal carcinoma, examining the role of adding bevacizumab to every-21-day carboplatin and paclitaxel. The objective was to examine whether mutations in homologous recombination genes affect response to treatment.

3 – Efficacy and safety of trabectedin or dacarbazine for the treatment of patients with uterine leiomyosarcoma after prior chemotherapy: A subgroup analysis of the randomized phase III SAR-3007 study

M.L. Hensleya, et al.

Study objectives: In ET743-SAR-3007, the efficacy of trabectedin in patients with advanced leiomyosarcoma (LMS) or liposarcoma (LPS), after chemotherapy failure, was compared with the active comparator dacarbazine. As reported, trabectedin exhibited improved disease control with median progression-free survival of 4.2 months (vs 1.5 months for dacarbazine) (HR 0.55; P less than .0001), with similar efficacy in both LMS and LPS cohorts. An analysis was conducted to assess the efficacy and safety of trabectedin or dacarbazine in the largest subgroup of the study, the 232 women with uterine LMS, who comprised 40.2% of the study participants.

10 – GOG 186H: A randomized phase II evaluation of weekly paclitaxel versus weekly paclitaxel with oncolytic reovirus in the treatment of recurrent or persistent ovarian, fallopian tube, or primary peritoneal cancer

D.E. Cohna, et al.

Study objectives: To assess whether the addition of oncolytic reovirus to weekly paclitaxel treatment prolonged progression-free survival in women with recurrent or persistent ovarian, tubal, or primary peritoneal cancer.

25 – Common single nucleotide polymorphisms associated with ovarian cancer risk contribute to the racial disparity in incidence

A. Berchucka, et al.

Study objectives: Data from the U.S. Surveillance, Epidemiology and End Results (SEER) registry have shown that ovarian cancer incidence is 35% lower in blacks than in whites. Differences in oophorectomy rates and epidemiologic risk factors such as parity and oral contraceptive use explain about 30% of this disparity. The Ovarian Cancer Association Consortium has identified 18 genome-wide significant common low-penetrance single nucleotide polymorphisms (SNPs) that increase ovarian cancer risk. Investigators examined whether these risk alleles are more common in whites than blacks to determine whether this contributes to the racial disparity in ovarian cancer incidence.

47 – A stratified randomized double-blind phase II trial of celecoxib in the treatment of patients with cervical intraepithelial neoplasia: A Gynecologic Oncology Group (GOG 0207) study with translational biomarkers and drug level monitoring

J.S. Radera, et al.

Study objectives: To examine the effect of celecoxib on cervical intraepithelial neoplasia type 3 based on whether or not the patient had regression of disease.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill.