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Society of Gynecologic Oncology (SGO): Annual Meeting on Women's Cancer
New light shed on olaparib therapy in ovarian cancer
CHICAGO – Olaparib improves outcomes in women with ovarian cancer who have a germline BRCA mutation, but its use at least as maintenance therapy is not cost-effective, according to research reported at the annual meeting of the Society of Gynecologic Oncology.
The Food and Drug Administration approved olaparib, an oral inhibitor of poly-ADP-ribose polymerase (PARP), in December 2014 for the treatment of patients who have recurrent ovarian cancer with a germline BRCA mutation and have received at least three prior lines of therapy. It is currently not approved for maintenance therapy in the United States.
Subsequent therapy may mask a survival benefit
In the first of three studies, investigators led by Dr. Ursula A. Matulonis performed a post hoc, exploratory analysis of data from a pivotal randomized phase II trial in platinum-sensitive relapsed ovarian cancer (Study 19). The trial, sponsored by AstraZeneca, compared olaparib (Lynparza) with placebo as maintenance therapy.
A previous stratified analysis among 265 patients revealed that those with a BRCA mutation had a marked progression-free survival benefit with olaparib versus placebo (11.2 vs. 4.3 months; hazard ratio, 0.18) but no significant gain in overall survival (34.9 vs. 31.9 months; hazard ratio, 0.73) (Lancet Oncol. 2014;15:852-61), according to Dr. Matulonis, medical director and program leader of the medical gynecologic oncology program at the Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School, both in Boston.
Crossover to olaparib was not permitted in the trial, but patients may have accessed PARP inhibitors outside of the study, she noted. “It was hypothesized that patients switching treatments may have reduced the beneficial impact of olaparib on the overall survival results. We know that switching is common in randomized trials in oncology but difficult to prevent practically and ethically, and it certainly may make an impact on overall survival.”
In the new, exploratory analysis, she and her colleagues reassessed outcomes after excluding all trial sites at which at least one patient received a PARP inhibitor after progression, which left 198 patients.
Results still showed a dramatic progression-free survival benefit for olaparib over placebo for those with a BRCA mutation (12.4 vs. 4.4 months; hazard ratio, 0.14). But now, olaparib also conferred a significant overall survival benefit, halving the risk of death (34.9 vs. 26.6 months; hazard ratio, 0.52), reported Dr. Matulonis, who disclosed that she has received research funding and speakers bureau remuneration from AstraZeneca.
“This change in overall survival hazard ratio may suggest a confounding influence that reduced the beneficial impact of olaparib,” she said. “There remains a degree of uncertainty owing to small sample sizes and lack of data maturity, so further analysis on more mature data is required to confirm these findings.”
Analysis confirms efficacy, safety in heavily pretreated patients
In the second study, Dr. Matulonis and colleagues performed a pooled analysis to assess the impact of olaparib in patients with advanced relapsed ovarian cancer having a germline BRCA mutation. Results were based on 273 patients given olaparib monotherapy in six AstraZeneca-sponsored phase I and II trials.
In the entire cohort, the overall response rate was 36% and the median duration of response was 7.4 months. The corresponding values were 31% and 7.8 months in the three-fourths of patients who had received at least three prior lines of chemotherapy.
Benefit was seen whether patients’ disease was platinum sensitive, resistant, or unknown, Dr. Matulonis reported. However, the response rate fell as the number of previous lines of therapy increased.
The rate of grade 3 or worse adverse events was 50% in the total population and 54% in the subset who received three or more previous therapies, and the rate of serious adverse events was 30% and 34%, respectively. Eight patients (all in the heavily pretreated group) had a serious adverse event leading to death, but none were considered causally related to olaparib.
“Olaparib treatment benefits were observed in all the patient subgroups,” Dr. Matulonis said. “The safety profile of olaparib was acceptable in patients who had received three or more prior lines of therapy.”
She noted that an ongoing series of phase III trials of monotherapy in patients with germline BRCA mutations – the Studies of Olaparib in Ovarian Cancer (SOLO) 1, 2, and 3 trials – should provide more information on use of the drug in various settings.
Invited discussant Dr. Elizabeth Swisher, medical director of the breast and ovarian cancer prevention program at the Seattle Cancer Care Alliance and professor in the gynecologic oncology division at the University of Washington, noted the uncertainty surrounding the optimal use of PARP inhibitors in ovarian cancer and mentioned that olaparib is approved as maintenance therapy in Europe.
“Many of you have probably been in the same situation that I have, where I have a patient in front of me and have to say, ‘Yes, this would be a good drug for you, but you need to fail a couple more lines of chemotherapy first,’ ” she said. “And we all know that later in the disease course, GI symptoms become more prominent and an oral drug may not be tolerated, so we might lose the opportunity to treat these patients with these drugs.”
Therefore, the field should address some key unanswered questions about PARP inhibitor therapy, according to Dr. Swisher: “Really, what is the best time point for using it – is it at maintenance, or is it at the time of relapse? And if we use it as maintenance, is it in the primary setting or the recurrent setting?” she elaborated.
She noted that women with somatic BRCA mutations as opposed to germline ones seem to benefit similarly from olaparib, but as insurance companies in the United States often resist covering tumor testing, this subset of women is often missed. “Predictors of response and resistance other than BRCA mutations are needed,” she added.
Models suggest maintenance therapy is not cost-effective
In the third study, investigators led by Dr. Haller J. Smith, a resident in obstetrics and gynecology at the University of Alabama, Birmingham, constructed models to assess the cost-effectiveness of olaparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer.
They used as a target population 5,549 women who had a complete response to primary therapy, experienced a recurrence, and then had at least a partial response to second-line chemotherapy. Analyses assumed a germline BRCA mutation prevalence of 20%.
In the model, patients received six cycles of chemotherapy, followed by either observation or olaparib maintenance therapy. The cost of olaparib was set at $7,000 per month, while the cost of observation was based on national guidelines and Medicare reimbursement rates. “The cost of adverse events was not included in the model as the majority of these in the phase II trial were grade 1 or 2,” Dr. Smith noted.
Results of the base case analysis showed that among patients with a BRCA mutation, the incremental cost-effectiveness ratio (ICER) for olaparib relative to observation was $135,672 per progression-free life-year saved – more than double the $50,000 threshold the investigators considered to be cost-effective, Dr. Smith reported. Among patients with wild type for BRCA, the ICER was sharply higher, at $315,840.
Sensitivity analyses showed that olaparib therapy was still not cost-effective when the prevalence of BRCA mutations and progression-free survival were varied. But the ICER fell to $97,404 when the cost of the drug was reduced to $5,000 and fell to $49,584 when it was reduced to $2,500.
“In order to achieve an ICER of less than $50,000, the cost of olaparib would have to be $2,500 or less per month,” Dr. Smith said. However, “in the era of molecular targeted therapies, an ICER of less than $100,000 would be considered by many to be cost-effective,” she acknowledged.
“While PARP inhibitors and other molecular targeted therapies represent exciting new therapeutic options for our patients, the costs associated with these drugs remain a significant concern. As health care costs continue to increase, cost-effectiveness studies are likely to become a more important part of the drug development and approval process,” she concluded.
CHICAGO – Olaparib improves outcomes in women with ovarian cancer who have a germline BRCA mutation, but its use at least as maintenance therapy is not cost-effective, according to research reported at the annual meeting of the Society of Gynecologic Oncology.
The Food and Drug Administration approved olaparib, an oral inhibitor of poly-ADP-ribose polymerase (PARP), in December 2014 for the treatment of patients who have recurrent ovarian cancer with a germline BRCA mutation and have received at least three prior lines of therapy. It is currently not approved for maintenance therapy in the United States.
Subsequent therapy may mask a survival benefit
In the first of three studies, investigators led by Dr. Ursula A. Matulonis performed a post hoc, exploratory analysis of data from a pivotal randomized phase II trial in platinum-sensitive relapsed ovarian cancer (Study 19). The trial, sponsored by AstraZeneca, compared olaparib (Lynparza) with placebo as maintenance therapy.
A previous stratified analysis among 265 patients revealed that those with a BRCA mutation had a marked progression-free survival benefit with olaparib versus placebo (11.2 vs. 4.3 months; hazard ratio, 0.18) but no significant gain in overall survival (34.9 vs. 31.9 months; hazard ratio, 0.73) (Lancet Oncol. 2014;15:852-61), according to Dr. Matulonis, medical director and program leader of the medical gynecologic oncology program at the Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School, both in Boston.
Crossover to olaparib was not permitted in the trial, but patients may have accessed PARP inhibitors outside of the study, she noted. “It was hypothesized that patients switching treatments may have reduced the beneficial impact of olaparib on the overall survival results. We know that switching is common in randomized trials in oncology but difficult to prevent practically and ethically, and it certainly may make an impact on overall survival.”
In the new, exploratory analysis, she and her colleagues reassessed outcomes after excluding all trial sites at which at least one patient received a PARP inhibitor after progression, which left 198 patients.
Results still showed a dramatic progression-free survival benefit for olaparib over placebo for those with a BRCA mutation (12.4 vs. 4.4 months; hazard ratio, 0.14). But now, olaparib also conferred a significant overall survival benefit, halving the risk of death (34.9 vs. 26.6 months; hazard ratio, 0.52), reported Dr. Matulonis, who disclosed that she has received research funding and speakers bureau remuneration from AstraZeneca.
“This change in overall survival hazard ratio may suggest a confounding influence that reduced the beneficial impact of olaparib,” she said. “There remains a degree of uncertainty owing to small sample sizes and lack of data maturity, so further analysis on more mature data is required to confirm these findings.”
Analysis confirms efficacy, safety in heavily pretreated patients
In the second study, Dr. Matulonis and colleagues performed a pooled analysis to assess the impact of olaparib in patients with advanced relapsed ovarian cancer having a germline BRCA mutation. Results were based on 273 patients given olaparib monotherapy in six AstraZeneca-sponsored phase I and II trials.
In the entire cohort, the overall response rate was 36% and the median duration of response was 7.4 months. The corresponding values were 31% and 7.8 months in the three-fourths of patients who had received at least three prior lines of chemotherapy.
Benefit was seen whether patients’ disease was platinum sensitive, resistant, or unknown, Dr. Matulonis reported. However, the response rate fell as the number of previous lines of therapy increased.
The rate of grade 3 or worse adverse events was 50% in the total population and 54% in the subset who received three or more previous therapies, and the rate of serious adverse events was 30% and 34%, respectively. Eight patients (all in the heavily pretreated group) had a serious adverse event leading to death, but none were considered causally related to olaparib.
“Olaparib treatment benefits were observed in all the patient subgroups,” Dr. Matulonis said. “The safety profile of olaparib was acceptable in patients who had received three or more prior lines of therapy.”
She noted that an ongoing series of phase III trials of monotherapy in patients with germline BRCA mutations – the Studies of Olaparib in Ovarian Cancer (SOLO) 1, 2, and 3 trials – should provide more information on use of the drug in various settings.
Invited discussant Dr. Elizabeth Swisher, medical director of the breast and ovarian cancer prevention program at the Seattle Cancer Care Alliance and professor in the gynecologic oncology division at the University of Washington, noted the uncertainty surrounding the optimal use of PARP inhibitors in ovarian cancer and mentioned that olaparib is approved as maintenance therapy in Europe.
“Many of you have probably been in the same situation that I have, where I have a patient in front of me and have to say, ‘Yes, this would be a good drug for you, but you need to fail a couple more lines of chemotherapy first,’ ” she said. “And we all know that later in the disease course, GI symptoms become more prominent and an oral drug may not be tolerated, so we might lose the opportunity to treat these patients with these drugs.”
Therefore, the field should address some key unanswered questions about PARP inhibitor therapy, according to Dr. Swisher: “Really, what is the best time point for using it – is it at maintenance, or is it at the time of relapse? And if we use it as maintenance, is it in the primary setting or the recurrent setting?” she elaborated.
She noted that women with somatic BRCA mutations as opposed to germline ones seem to benefit similarly from olaparib, but as insurance companies in the United States often resist covering tumor testing, this subset of women is often missed. “Predictors of response and resistance other than BRCA mutations are needed,” she added.
Models suggest maintenance therapy is not cost-effective
In the third study, investigators led by Dr. Haller J. Smith, a resident in obstetrics and gynecology at the University of Alabama, Birmingham, constructed models to assess the cost-effectiveness of olaparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer.
They used as a target population 5,549 women who had a complete response to primary therapy, experienced a recurrence, and then had at least a partial response to second-line chemotherapy. Analyses assumed a germline BRCA mutation prevalence of 20%.
In the model, patients received six cycles of chemotherapy, followed by either observation or olaparib maintenance therapy. The cost of olaparib was set at $7,000 per month, while the cost of observation was based on national guidelines and Medicare reimbursement rates. “The cost of adverse events was not included in the model as the majority of these in the phase II trial were grade 1 or 2,” Dr. Smith noted.
Results of the base case analysis showed that among patients with a BRCA mutation, the incremental cost-effectiveness ratio (ICER) for olaparib relative to observation was $135,672 per progression-free life-year saved – more than double the $50,000 threshold the investigators considered to be cost-effective, Dr. Smith reported. Among patients with wild type for BRCA, the ICER was sharply higher, at $315,840.
Sensitivity analyses showed that olaparib therapy was still not cost-effective when the prevalence of BRCA mutations and progression-free survival were varied. But the ICER fell to $97,404 when the cost of the drug was reduced to $5,000 and fell to $49,584 when it was reduced to $2,500.
“In order to achieve an ICER of less than $50,000, the cost of olaparib would have to be $2,500 or less per month,” Dr. Smith said. However, “in the era of molecular targeted therapies, an ICER of less than $100,000 would be considered by many to be cost-effective,” she acknowledged.
“While PARP inhibitors and other molecular targeted therapies represent exciting new therapeutic options for our patients, the costs associated with these drugs remain a significant concern. As health care costs continue to increase, cost-effectiveness studies are likely to become a more important part of the drug development and approval process,” she concluded.
CHICAGO – Olaparib improves outcomes in women with ovarian cancer who have a germline BRCA mutation, but its use at least as maintenance therapy is not cost-effective, according to research reported at the annual meeting of the Society of Gynecologic Oncology.
The Food and Drug Administration approved olaparib, an oral inhibitor of poly-ADP-ribose polymerase (PARP), in December 2014 for the treatment of patients who have recurrent ovarian cancer with a germline BRCA mutation and have received at least three prior lines of therapy. It is currently not approved for maintenance therapy in the United States.
Subsequent therapy may mask a survival benefit
In the first of three studies, investigators led by Dr. Ursula A. Matulonis performed a post hoc, exploratory analysis of data from a pivotal randomized phase II trial in platinum-sensitive relapsed ovarian cancer (Study 19). The trial, sponsored by AstraZeneca, compared olaparib (Lynparza) with placebo as maintenance therapy.
A previous stratified analysis among 265 patients revealed that those with a BRCA mutation had a marked progression-free survival benefit with olaparib versus placebo (11.2 vs. 4.3 months; hazard ratio, 0.18) but no significant gain in overall survival (34.9 vs. 31.9 months; hazard ratio, 0.73) (Lancet Oncol. 2014;15:852-61), according to Dr. Matulonis, medical director and program leader of the medical gynecologic oncology program at the Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School, both in Boston.
Crossover to olaparib was not permitted in the trial, but patients may have accessed PARP inhibitors outside of the study, she noted. “It was hypothesized that patients switching treatments may have reduced the beneficial impact of olaparib on the overall survival results. We know that switching is common in randomized trials in oncology but difficult to prevent practically and ethically, and it certainly may make an impact on overall survival.”
In the new, exploratory analysis, she and her colleagues reassessed outcomes after excluding all trial sites at which at least one patient received a PARP inhibitor after progression, which left 198 patients.
Results still showed a dramatic progression-free survival benefit for olaparib over placebo for those with a BRCA mutation (12.4 vs. 4.4 months; hazard ratio, 0.14). But now, olaparib also conferred a significant overall survival benefit, halving the risk of death (34.9 vs. 26.6 months; hazard ratio, 0.52), reported Dr. Matulonis, who disclosed that she has received research funding and speakers bureau remuneration from AstraZeneca.
“This change in overall survival hazard ratio may suggest a confounding influence that reduced the beneficial impact of olaparib,” she said. “There remains a degree of uncertainty owing to small sample sizes and lack of data maturity, so further analysis on more mature data is required to confirm these findings.”
Analysis confirms efficacy, safety in heavily pretreated patients
In the second study, Dr. Matulonis and colleagues performed a pooled analysis to assess the impact of olaparib in patients with advanced relapsed ovarian cancer having a germline BRCA mutation. Results were based on 273 patients given olaparib monotherapy in six AstraZeneca-sponsored phase I and II trials.
In the entire cohort, the overall response rate was 36% and the median duration of response was 7.4 months. The corresponding values were 31% and 7.8 months in the three-fourths of patients who had received at least three prior lines of chemotherapy.
Benefit was seen whether patients’ disease was platinum sensitive, resistant, or unknown, Dr. Matulonis reported. However, the response rate fell as the number of previous lines of therapy increased.
The rate of grade 3 or worse adverse events was 50% in the total population and 54% in the subset who received three or more previous therapies, and the rate of serious adverse events was 30% and 34%, respectively. Eight patients (all in the heavily pretreated group) had a serious adverse event leading to death, but none were considered causally related to olaparib.
“Olaparib treatment benefits were observed in all the patient subgroups,” Dr. Matulonis said. “The safety profile of olaparib was acceptable in patients who had received three or more prior lines of therapy.”
She noted that an ongoing series of phase III trials of monotherapy in patients with germline BRCA mutations – the Studies of Olaparib in Ovarian Cancer (SOLO) 1, 2, and 3 trials – should provide more information on use of the drug in various settings.
Invited discussant Dr. Elizabeth Swisher, medical director of the breast and ovarian cancer prevention program at the Seattle Cancer Care Alliance and professor in the gynecologic oncology division at the University of Washington, noted the uncertainty surrounding the optimal use of PARP inhibitors in ovarian cancer and mentioned that olaparib is approved as maintenance therapy in Europe.
“Many of you have probably been in the same situation that I have, where I have a patient in front of me and have to say, ‘Yes, this would be a good drug for you, but you need to fail a couple more lines of chemotherapy first,’ ” she said. “And we all know that later in the disease course, GI symptoms become more prominent and an oral drug may not be tolerated, so we might lose the opportunity to treat these patients with these drugs.”
Therefore, the field should address some key unanswered questions about PARP inhibitor therapy, according to Dr. Swisher: “Really, what is the best time point for using it – is it at maintenance, or is it at the time of relapse? And if we use it as maintenance, is it in the primary setting or the recurrent setting?” she elaborated.
She noted that women with somatic BRCA mutations as opposed to germline ones seem to benefit similarly from olaparib, but as insurance companies in the United States often resist covering tumor testing, this subset of women is often missed. “Predictors of response and resistance other than BRCA mutations are needed,” she added.
Models suggest maintenance therapy is not cost-effective
In the third study, investigators led by Dr. Haller J. Smith, a resident in obstetrics and gynecology at the University of Alabama, Birmingham, constructed models to assess the cost-effectiveness of olaparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer.
They used as a target population 5,549 women who had a complete response to primary therapy, experienced a recurrence, and then had at least a partial response to second-line chemotherapy. Analyses assumed a germline BRCA mutation prevalence of 20%.
In the model, patients received six cycles of chemotherapy, followed by either observation or olaparib maintenance therapy. The cost of olaparib was set at $7,000 per month, while the cost of observation was based on national guidelines and Medicare reimbursement rates. “The cost of adverse events was not included in the model as the majority of these in the phase II trial were grade 1 or 2,” Dr. Smith noted.
Results of the base case analysis showed that among patients with a BRCA mutation, the incremental cost-effectiveness ratio (ICER) for olaparib relative to observation was $135,672 per progression-free life-year saved – more than double the $50,000 threshold the investigators considered to be cost-effective, Dr. Smith reported. Among patients with wild type for BRCA, the ICER was sharply higher, at $315,840.
Sensitivity analyses showed that olaparib therapy was still not cost-effective when the prevalence of BRCA mutations and progression-free survival were varied. But the ICER fell to $97,404 when the cost of the drug was reduced to $5,000 and fell to $49,584 when it was reduced to $2,500.
“In order to achieve an ICER of less than $50,000, the cost of olaparib would have to be $2,500 or less per month,” Dr. Smith said. However, “in the era of molecular targeted therapies, an ICER of less than $100,000 would be considered by many to be cost-effective,” she acknowledged.
“While PARP inhibitors and other molecular targeted therapies represent exciting new therapeutic options for our patients, the costs associated with these drugs remain a significant concern. As health care costs continue to increase, cost-effectiveness studies are likely to become a more important part of the drug development and approval process,” she concluded.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Circulating tumor cells prognostic in advanced cervical cancer
CHICAGO – Circulating tumor cells are a prognostic biomarker for overall survival in women with advanced cervical cancer who are receiving chemotherapy with or without bevacizumab, according to an analysis of the Gynecologic Oncology Group’s 240 trial.
The risk of death among patients given cisplatin-paclitaxel plus bevacizumab was reduced by 10% for those who had a higher pretreatment level of circulating tumor cells (CTCs) and by 13% for those who had a greater treatment-related decline in CTCs, Dr. Krishnansu S. Tewari reported at the annual meeting of the Society of Gynecologic Oncology.
“We can predict that leaky vasculature resulting from tumor angiogenesis may permit systemic distribution of CTCs through intratumoral vascular shunting, and the vulnerability to anti-angiogenesis therapies may be due to this increased vascularization,” said Dr. Tewari of UC Irvine Health in Orange, Calif.
In comments provided by e-mail, session comoderator Dr. Charles N. Landen Jr. of the University of Virginia, Charlottesville, said that the study is important in that it demonstrates the feasibility of using CTCs as a biomarker in this setting, but its results are not practice changing.
“If you had a decrease in CTCs, you were more likely to have a good response to therapy. However, this was not any better at detecting response than conventional methods such as a CT scan,” he explained.
Giving some background to the research, Dr. Tewari said that “it’s difficult to monitor response in patients with advanced cervical cancer. Doing imaging studies after every two cycles is expensive, and there are no validated serum tumor markers in this disease. In addition, tumor is not often accessible for interrogation to help guide subsequent therapy when patients ultimately progress on anti-VEGF [vascular endothelial growth factor] therapy. Finally, predictive biomarkers are lacking in advanced cervical cancer.”
“CTCs can be seen as minimally invasive liquid biopsies, and their presence in breast cancer, prostate cancer, and non–small cell lung cancer has been correlated with survival,” he noted. “However, all three of those solid tumors are known to spread hematogenously. While hematogenous spread can occur in cervical cancer, it is felt to be rare.”
The phase III trial enrolled women with recurrent, persistent, or metastatic cervical cancer and tested the addition of bevacizumab (Avastin, manufactured by Genentech/Roche) to doublet chemotherapy (cisplatin-paclitaxel or topotecan-paclitaxel) given on 21-day cycles. Main results showed a significant gain in overall survival from the addition of bevacizumab (N. Engl. J. Med. 2014;370:734-43), leading to regulatory approval of combination therapy in the United States and elsewhere.
The new analysis focused on the 174 women (39%) in the trial who had 8.5 mL of whole blood collected for CTC measurement before starting the first cycle of therapy and, in most cases, again 36 days after the first cycle.
The investigators were able to identify CTCs for 97% of patients in the pretreatment sample and for 81% in the post-treatment sample, Dr. Tewari noted.
Results showed that the median CTC count in the sample fell from seven cells pretreatment to four cells post-treatment (P < .0001). Of note, there was no correlation with the response to treatment according to RECIST (Response Evaluation Criteria in Solid Tumors).
Patients with high (above-median) pretreatment levels of CTCs had significantly better median progression-free survival with bevacizumab than without it (10.8 vs. 6.9 months; hazard ratio [HR], 0.59). In contrast, there was no significant benefit for patients with low (below-median) pretreatment levels of CTCs (7.3 and 6.2 months).
Among patients given cisplatin-paclitaxel plus bevacizumab, the higher the pretreatment CTC level, the lower the risk of death (HR, 0.90). Among patients given cisplatin-paclitaxel overall, the higher the post-treatment CTC level, the greater the risk of death (HR, 1.12), Dr. Tewari reported.
Finally, the greater the decline in CTCs from before to after treatment in patients given cisplatin-paclitaxel plus bevacizumab, the lower the risk of death (HR, 0.87), he said.
Dr. Tewari disclosed that he is a consultant to Genentech/Roche, Advaxis, and Caris Life Sciences; receives honoraria/reimbursement or grants from Genentech/Roche; and performs research for Caris Life Sciences.
CHICAGO – Circulating tumor cells are a prognostic biomarker for overall survival in women with advanced cervical cancer who are receiving chemotherapy with or without bevacizumab, according to an analysis of the Gynecologic Oncology Group’s 240 trial.
The risk of death among patients given cisplatin-paclitaxel plus bevacizumab was reduced by 10% for those who had a higher pretreatment level of circulating tumor cells (CTCs) and by 13% for those who had a greater treatment-related decline in CTCs, Dr. Krishnansu S. Tewari reported at the annual meeting of the Society of Gynecologic Oncology.
“We can predict that leaky vasculature resulting from tumor angiogenesis may permit systemic distribution of CTCs through intratumoral vascular shunting, and the vulnerability to anti-angiogenesis therapies may be due to this increased vascularization,” said Dr. Tewari of UC Irvine Health in Orange, Calif.
In comments provided by e-mail, session comoderator Dr. Charles N. Landen Jr. of the University of Virginia, Charlottesville, said that the study is important in that it demonstrates the feasibility of using CTCs as a biomarker in this setting, but its results are not practice changing.
“If you had a decrease in CTCs, you were more likely to have a good response to therapy. However, this was not any better at detecting response than conventional methods such as a CT scan,” he explained.
Giving some background to the research, Dr. Tewari said that “it’s difficult to monitor response in patients with advanced cervical cancer. Doing imaging studies after every two cycles is expensive, and there are no validated serum tumor markers in this disease. In addition, tumor is not often accessible for interrogation to help guide subsequent therapy when patients ultimately progress on anti-VEGF [vascular endothelial growth factor] therapy. Finally, predictive biomarkers are lacking in advanced cervical cancer.”
“CTCs can be seen as minimally invasive liquid biopsies, and their presence in breast cancer, prostate cancer, and non–small cell lung cancer has been correlated with survival,” he noted. “However, all three of those solid tumors are known to spread hematogenously. While hematogenous spread can occur in cervical cancer, it is felt to be rare.”
The phase III trial enrolled women with recurrent, persistent, or metastatic cervical cancer and tested the addition of bevacizumab (Avastin, manufactured by Genentech/Roche) to doublet chemotherapy (cisplatin-paclitaxel or topotecan-paclitaxel) given on 21-day cycles. Main results showed a significant gain in overall survival from the addition of bevacizumab (N. Engl. J. Med. 2014;370:734-43), leading to regulatory approval of combination therapy in the United States and elsewhere.
The new analysis focused on the 174 women (39%) in the trial who had 8.5 mL of whole blood collected for CTC measurement before starting the first cycle of therapy and, in most cases, again 36 days after the first cycle.
The investigators were able to identify CTCs for 97% of patients in the pretreatment sample and for 81% in the post-treatment sample, Dr. Tewari noted.
Results showed that the median CTC count in the sample fell from seven cells pretreatment to four cells post-treatment (P < .0001). Of note, there was no correlation with the response to treatment according to RECIST (Response Evaluation Criteria in Solid Tumors).
Patients with high (above-median) pretreatment levels of CTCs had significantly better median progression-free survival with bevacizumab than without it (10.8 vs. 6.9 months; hazard ratio [HR], 0.59). In contrast, there was no significant benefit for patients with low (below-median) pretreatment levels of CTCs (7.3 and 6.2 months).
Among patients given cisplatin-paclitaxel plus bevacizumab, the higher the pretreatment CTC level, the lower the risk of death (HR, 0.90). Among patients given cisplatin-paclitaxel overall, the higher the post-treatment CTC level, the greater the risk of death (HR, 1.12), Dr. Tewari reported.
Finally, the greater the decline in CTCs from before to after treatment in patients given cisplatin-paclitaxel plus bevacizumab, the lower the risk of death (HR, 0.87), he said.
Dr. Tewari disclosed that he is a consultant to Genentech/Roche, Advaxis, and Caris Life Sciences; receives honoraria/reimbursement or grants from Genentech/Roche; and performs research for Caris Life Sciences.
CHICAGO – Circulating tumor cells are a prognostic biomarker for overall survival in women with advanced cervical cancer who are receiving chemotherapy with or without bevacizumab, according to an analysis of the Gynecologic Oncology Group’s 240 trial.
The risk of death among patients given cisplatin-paclitaxel plus bevacizumab was reduced by 10% for those who had a higher pretreatment level of circulating tumor cells (CTCs) and by 13% for those who had a greater treatment-related decline in CTCs, Dr. Krishnansu S. Tewari reported at the annual meeting of the Society of Gynecologic Oncology.
“We can predict that leaky vasculature resulting from tumor angiogenesis may permit systemic distribution of CTCs through intratumoral vascular shunting, and the vulnerability to anti-angiogenesis therapies may be due to this increased vascularization,” said Dr. Tewari of UC Irvine Health in Orange, Calif.
In comments provided by e-mail, session comoderator Dr. Charles N. Landen Jr. of the University of Virginia, Charlottesville, said that the study is important in that it demonstrates the feasibility of using CTCs as a biomarker in this setting, but its results are not practice changing.
“If you had a decrease in CTCs, you were more likely to have a good response to therapy. However, this was not any better at detecting response than conventional methods such as a CT scan,” he explained.
Giving some background to the research, Dr. Tewari said that “it’s difficult to monitor response in patients with advanced cervical cancer. Doing imaging studies after every two cycles is expensive, and there are no validated serum tumor markers in this disease. In addition, tumor is not often accessible for interrogation to help guide subsequent therapy when patients ultimately progress on anti-VEGF [vascular endothelial growth factor] therapy. Finally, predictive biomarkers are lacking in advanced cervical cancer.”
“CTCs can be seen as minimally invasive liquid biopsies, and their presence in breast cancer, prostate cancer, and non–small cell lung cancer has been correlated with survival,” he noted. “However, all three of those solid tumors are known to spread hematogenously. While hematogenous spread can occur in cervical cancer, it is felt to be rare.”
The phase III trial enrolled women with recurrent, persistent, or metastatic cervical cancer and tested the addition of bevacizumab (Avastin, manufactured by Genentech/Roche) to doublet chemotherapy (cisplatin-paclitaxel or topotecan-paclitaxel) given on 21-day cycles. Main results showed a significant gain in overall survival from the addition of bevacizumab (N. Engl. J. Med. 2014;370:734-43), leading to regulatory approval of combination therapy in the United States and elsewhere.
The new analysis focused on the 174 women (39%) in the trial who had 8.5 mL of whole blood collected for CTC measurement before starting the first cycle of therapy and, in most cases, again 36 days after the first cycle.
The investigators were able to identify CTCs for 97% of patients in the pretreatment sample and for 81% in the post-treatment sample, Dr. Tewari noted.
Results showed that the median CTC count in the sample fell from seven cells pretreatment to four cells post-treatment (P < .0001). Of note, there was no correlation with the response to treatment according to RECIST (Response Evaluation Criteria in Solid Tumors).
Patients with high (above-median) pretreatment levels of CTCs had significantly better median progression-free survival with bevacizumab than without it (10.8 vs. 6.9 months; hazard ratio [HR], 0.59). In contrast, there was no significant benefit for patients with low (below-median) pretreatment levels of CTCs (7.3 and 6.2 months).
Among patients given cisplatin-paclitaxel plus bevacizumab, the higher the pretreatment CTC level, the lower the risk of death (HR, 0.90). Among patients given cisplatin-paclitaxel overall, the higher the post-treatment CTC level, the greater the risk of death (HR, 1.12), Dr. Tewari reported.
Finally, the greater the decline in CTCs from before to after treatment in patients given cisplatin-paclitaxel plus bevacizumab, the lower the risk of death (HR, 0.87), he said.
Dr. Tewari disclosed that he is a consultant to Genentech/Roche, Advaxis, and Caris Life Sciences; receives honoraria/reimbursement or grants from Genentech/Roche; and performs research for Caris Life Sciences.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: CTCs provide prognostic information in women being treated for advanced cervical cancer.
Major finding: Risk of death for patients given cisplatin-paclitaxel plus bevacizumab was reduced by 10% for those who had a high pretreatment level of CTCs and by 13% for those who had a greater treatment-related decline in CTCs.
Data source: Analysis of 174 women with advanced cervical cancer given chemotherapy with or without bevacizumab in a phase III trial.
Disclosures: Dr. Tewari disclosed that he is a consultant to Genentech/Roche, Advaxis, and Caris Life Sciences; receives honoraria/reimbursement or grants from Genentech/Roche; and performs research for Caris Life Sciences.
Sentinel node mapping adequately detects nodal spread of endometrial cancer
CHICAGO – Sentinel lymph node mapping is a safe, less extensive alternative to lymph node dissection in women with endometrial cancer regardless of the clinically suspected risk of metastases, suggest a pair of retrospective cohort studies reported at the annual meeting of the Society of Gynecologic Oncology.
“The role and extent of surgical staging in endometrial carcinoma is controversial. The various strategies range from no lymphadenectomy to a full lymphadenectomy dissection up to the renal vessels,” said Dr. Ane Gerda Zahl Eriksson, a surgical fellow in gynecologic oncology at the Memorial Sloan Kettering Cancer Center, New York.
“The use of SLN [sentinel lymph node] mapping is emerging as an acceptable approach for nodal assessment in endometrial carcinoma. However, as always when introducing a novel management strategy, we must be mindful not to compromise oncologic outcome or otherwise inflict harm on our patients by our approach,” she added.
Dr. Eriksson and colleagues assessed clinicopathologic outcomes according to nodal assessment approach among women with low-risk endometrial cancer, defined as that with endometrioid histology of any grade with myometrial invasion of less than 50%.
They compared 493 women who had selective lymph node dissection (LND) at the Mayo Clinic between 2004 and 2008 according to an institutional algorithm (complete pelvic and para-aortic lymphadenectomy to the renal veins in cases deemed at risk for nodal metastasis) with 642 women who had SLN mapping at the Memorial Sloan Kettering Cancer Center between 2006 and 2013 according to an institutional algorithm. The SLNs were evaluated by pathologic ultrastaging and were considered positive whether they had macrometastases, micrometastases, or isolated tumor cells.
Results showed that patients in the SLN cohort were more likely to have pelvic nodes excised (93% vs. 58%) and less likely to have para-aortic nodes excised (14% vs. 50%), Dr. Eriksson reported.
Markedly fewer lymph nodes were removed per patient with the SLN algorithm, yet it yielded a higher detection rate of stage IIIC1 disease (4.8% vs. 1.8%) and similar detection rates of stage IIIA/B and stage IIIC2 disease.
Patients in the SLN cohort were more than twice as likely to receive adjuvant therapy (27% vs. 12%). (Dr. Eriksson noted that patients in the SLN cohort who had positive nodes were offered the same adjuvant therapy options regardless of the amount of metastases found in the nodes.)
With a median follow-up of 2.1 years in the SLN cohort and 3.5 years in the LND cohort, the cohorts had statistically indistinguishable 3-year rates of freedom from isolated nodal recurrence (99.6% in each) and disease-free survival (94.9% and 96.8%).
“The application of the SLN algorithm does not appear to compromise oncologic outcome in this short follow-up. The value of SLN dissection or selective lymphadenectomy in patients with tumors equal to or less than 2 cm remains controversial,” Dr. Eriksson commented. “The clinical significance of disease detected on ultrastaging and the role of adjuvant therapy in these patients remains to be determined.”
“Prospective assessment of the SLN algorithm is needed and underway,” she concluded. “Our findings support the use of either strategy for endometrial cancer staging with no apparent detriment to the SLN algorithm.”
In the second study, investigators led by Dr. Jennifer A. Ducie, also a surgical fellow in gynecologic oncology at the Memorial Sloan Kettering Cancer Center, performed a similar analysis among women with intermediate-risk endometrial cancer, defined as that having endometrioid histology with any grade and at least 50% myometrial invasion, and high-risk endometrial cancer, defined as serous or clear cell carcinoma.
In the intermediate-risk group, there were 82 patients in the SLN cohort and 107 patients in the LND cohort. The groups had a similar detection rate of stage IIIC disease overall (35% and 28%), but the SLN cohort had a higher rate of detection of stage IIIC1 disease (32% vs. 11%) and the LND cohort had a higher rate of detection of stage IIIC2 disease (17% vs. 4%), Dr. Ducie reported.
In the high-risk group, there were 120 patients in the SLN cohort and 103 patients in the LND cohort. Patients in the SLN cohort were more likely to have pelvic nodes removed (98% vs. 85%) but had fewer nodes removed (11 vs. 30). Among patients who had para-aortic nodes removed, the SLN cohort was similarly as likely as the LND cohort to have positive nodes, but had a smaller median number positive (two vs. five). The rate of detection of stage IIIC disease overall (23% vs. 19%) and of the substages was statistically indistinguishable.
“Though both strategies yield similar detection rates of stage IIIC disease, it remains to be determined if removal of more normal-appearing lymph nodes will improve survival,” Dr. Ducie concluded. “A limitation of this portion of our collaborative study is that we don’t address adjuvant therapy or outcomes, but these will be addressed in future analyses.”
CHICAGO – Sentinel lymph node mapping is a safe, less extensive alternative to lymph node dissection in women with endometrial cancer regardless of the clinically suspected risk of metastases, suggest a pair of retrospective cohort studies reported at the annual meeting of the Society of Gynecologic Oncology.
“The role and extent of surgical staging in endometrial carcinoma is controversial. The various strategies range from no lymphadenectomy to a full lymphadenectomy dissection up to the renal vessels,” said Dr. Ane Gerda Zahl Eriksson, a surgical fellow in gynecologic oncology at the Memorial Sloan Kettering Cancer Center, New York.
“The use of SLN [sentinel lymph node] mapping is emerging as an acceptable approach for nodal assessment in endometrial carcinoma. However, as always when introducing a novel management strategy, we must be mindful not to compromise oncologic outcome or otherwise inflict harm on our patients by our approach,” she added.
Dr. Eriksson and colleagues assessed clinicopathologic outcomes according to nodal assessment approach among women with low-risk endometrial cancer, defined as that with endometrioid histology of any grade with myometrial invasion of less than 50%.
They compared 493 women who had selective lymph node dissection (LND) at the Mayo Clinic between 2004 and 2008 according to an institutional algorithm (complete pelvic and para-aortic lymphadenectomy to the renal veins in cases deemed at risk for nodal metastasis) with 642 women who had SLN mapping at the Memorial Sloan Kettering Cancer Center between 2006 and 2013 according to an institutional algorithm. The SLNs were evaluated by pathologic ultrastaging and were considered positive whether they had macrometastases, micrometastases, or isolated tumor cells.
Results showed that patients in the SLN cohort were more likely to have pelvic nodes excised (93% vs. 58%) and less likely to have para-aortic nodes excised (14% vs. 50%), Dr. Eriksson reported.
Markedly fewer lymph nodes were removed per patient with the SLN algorithm, yet it yielded a higher detection rate of stage IIIC1 disease (4.8% vs. 1.8%) and similar detection rates of stage IIIA/B and stage IIIC2 disease.
Patients in the SLN cohort were more than twice as likely to receive adjuvant therapy (27% vs. 12%). (Dr. Eriksson noted that patients in the SLN cohort who had positive nodes were offered the same adjuvant therapy options regardless of the amount of metastases found in the nodes.)
With a median follow-up of 2.1 years in the SLN cohort and 3.5 years in the LND cohort, the cohorts had statistically indistinguishable 3-year rates of freedom from isolated nodal recurrence (99.6% in each) and disease-free survival (94.9% and 96.8%).
“The application of the SLN algorithm does not appear to compromise oncologic outcome in this short follow-up. The value of SLN dissection or selective lymphadenectomy in patients with tumors equal to or less than 2 cm remains controversial,” Dr. Eriksson commented. “The clinical significance of disease detected on ultrastaging and the role of adjuvant therapy in these patients remains to be determined.”
“Prospective assessment of the SLN algorithm is needed and underway,” she concluded. “Our findings support the use of either strategy for endometrial cancer staging with no apparent detriment to the SLN algorithm.”
In the second study, investigators led by Dr. Jennifer A. Ducie, also a surgical fellow in gynecologic oncology at the Memorial Sloan Kettering Cancer Center, performed a similar analysis among women with intermediate-risk endometrial cancer, defined as that having endometrioid histology with any grade and at least 50% myometrial invasion, and high-risk endometrial cancer, defined as serous or clear cell carcinoma.
In the intermediate-risk group, there were 82 patients in the SLN cohort and 107 patients in the LND cohort. The groups had a similar detection rate of stage IIIC disease overall (35% and 28%), but the SLN cohort had a higher rate of detection of stage IIIC1 disease (32% vs. 11%) and the LND cohort had a higher rate of detection of stage IIIC2 disease (17% vs. 4%), Dr. Ducie reported.
In the high-risk group, there were 120 patients in the SLN cohort and 103 patients in the LND cohort. Patients in the SLN cohort were more likely to have pelvic nodes removed (98% vs. 85%) but had fewer nodes removed (11 vs. 30). Among patients who had para-aortic nodes removed, the SLN cohort was similarly as likely as the LND cohort to have positive nodes, but had a smaller median number positive (two vs. five). The rate of detection of stage IIIC disease overall (23% vs. 19%) and of the substages was statistically indistinguishable.
“Though both strategies yield similar detection rates of stage IIIC disease, it remains to be determined if removal of more normal-appearing lymph nodes will improve survival,” Dr. Ducie concluded. “A limitation of this portion of our collaborative study is that we don’t address adjuvant therapy or outcomes, but these will be addressed in future analyses.”
CHICAGO – Sentinel lymph node mapping is a safe, less extensive alternative to lymph node dissection in women with endometrial cancer regardless of the clinically suspected risk of metastases, suggest a pair of retrospective cohort studies reported at the annual meeting of the Society of Gynecologic Oncology.
“The role and extent of surgical staging in endometrial carcinoma is controversial. The various strategies range from no lymphadenectomy to a full lymphadenectomy dissection up to the renal vessels,” said Dr. Ane Gerda Zahl Eriksson, a surgical fellow in gynecologic oncology at the Memorial Sloan Kettering Cancer Center, New York.
“The use of SLN [sentinel lymph node] mapping is emerging as an acceptable approach for nodal assessment in endometrial carcinoma. However, as always when introducing a novel management strategy, we must be mindful not to compromise oncologic outcome or otherwise inflict harm on our patients by our approach,” she added.
Dr. Eriksson and colleagues assessed clinicopathologic outcomes according to nodal assessment approach among women with low-risk endometrial cancer, defined as that with endometrioid histology of any grade with myometrial invasion of less than 50%.
They compared 493 women who had selective lymph node dissection (LND) at the Mayo Clinic between 2004 and 2008 according to an institutional algorithm (complete pelvic and para-aortic lymphadenectomy to the renal veins in cases deemed at risk for nodal metastasis) with 642 women who had SLN mapping at the Memorial Sloan Kettering Cancer Center between 2006 and 2013 according to an institutional algorithm. The SLNs were evaluated by pathologic ultrastaging and were considered positive whether they had macrometastases, micrometastases, or isolated tumor cells.
Results showed that patients in the SLN cohort were more likely to have pelvic nodes excised (93% vs. 58%) and less likely to have para-aortic nodes excised (14% vs. 50%), Dr. Eriksson reported.
Markedly fewer lymph nodes were removed per patient with the SLN algorithm, yet it yielded a higher detection rate of stage IIIC1 disease (4.8% vs. 1.8%) and similar detection rates of stage IIIA/B and stage IIIC2 disease.
Patients in the SLN cohort were more than twice as likely to receive adjuvant therapy (27% vs. 12%). (Dr. Eriksson noted that patients in the SLN cohort who had positive nodes were offered the same adjuvant therapy options regardless of the amount of metastases found in the nodes.)
With a median follow-up of 2.1 years in the SLN cohort and 3.5 years in the LND cohort, the cohorts had statistically indistinguishable 3-year rates of freedom from isolated nodal recurrence (99.6% in each) and disease-free survival (94.9% and 96.8%).
“The application of the SLN algorithm does not appear to compromise oncologic outcome in this short follow-up. The value of SLN dissection or selective lymphadenectomy in patients with tumors equal to or less than 2 cm remains controversial,” Dr. Eriksson commented. “The clinical significance of disease detected on ultrastaging and the role of adjuvant therapy in these patients remains to be determined.”
“Prospective assessment of the SLN algorithm is needed and underway,” she concluded. “Our findings support the use of either strategy for endometrial cancer staging with no apparent detriment to the SLN algorithm.”
In the second study, investigators led by Dr. Jennifer A. Ducie, also a surgical fellow in gynecologic oncology at the Memorial Sloan Kettering Cancer Center, performed a similar analysis among women with intermediate-risk endometrial cancer, defined as that having endometrioid histology with any grade and at least 50% myometrial invasion, and high-risk endometrial cancer, defined as serous or clear cell carcinoma.
In the intermediate-risk group, there were 82 patients in the SLN cohort and 107 patients in the LND cohort. The groups had a similar detection rate of stage IIIC disease overall (35% and 28%), but the SLN cohort had a higher rate of detection of stage IIIC1 disease (32% vs. 11%) and the LND cohort had a higher rate of detection of stage IIIC2 disease (17% vs. 4%), Dr. Ducie reported.
In the high-risk group, there were 120 patients in the SLN cohort and 103 patients in the LND cohort. Patients in the SLN cohort were more likely to have pelvic nodes removed (98% vs. 85%) but had fewer nodes removed (11 vs. 30). Among patients who had para-aortic nodes removed, the SLN cohort was similarly as likely as the LND cohort to have positive nodes, but had a smaller median number positive (two vs. five). The rate of detection of stage IIIC disease overall (23% vs. 19%) and of the substages was statistically indistinguishable.
“Though both strategies yield similar detection rates of stage IIIC disease, it remains to be determined if removal of more normal-appearing lymph nodes will improve survival,” Dr. Ducie concluded. “A limitation of this portion of our collaborative study is that we don’t address adjuvant therapy or outcomes, but these will be addressed in future analyses.”
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: SLN mapping performs similarly to LND for detecting stage IIIC disease in women with endometrial cancer.
Major finding: SLN mapping had a higher detection rate of stage IIIC1 disease in low-risk disease (4.8% vs. 1.8%) and a similar detection rate of stage IIIC disease overall in intermediate- and high-risk disease.
Data source: Two retrospective cohort studies of 1,135 women with low-risk endometrial cancer and 412 women with intermediate- or high-risk endometrial cancer.
Disclosures: Dr. Eriksson disclosed that she had no relevant conflicts of interest. Dr. Ducie disclosed that she had no relevant conflicts of interest.
New 9-valent HPV vaccine is efficacious, well tolerated
CHICAGO – The 9-valent human papillomavirus (HPV) vaccine recently approved by the Food and Drug Administration has high efficacy for preventing disease caused by the vaccine-covered viral types and is well tolerated, according to end-of study data from a randomized trial.
The vaccine was on par with the quadrivalent vaccine when it came to protection against infection with the four original viral types covered by both vaccines. Additionally, for the five new viral types, it was associated with a 97% reduction in all cervical, vaginal, and vulvar intraepithelial neoplasia, a 100% reduction in cervical intraepithelial neoplasia 3, and a more than 90% reduction in related procedures and treatments, investigators reported at the Annual meeting of Society of Gynecologic Oncology. Meanwhile, it had a good safety profile.
“The consistency of the data is very reassuring,” said Dr. Elmar A. Joura of the Medical University of Vienna, General Hospital, and Comprehensive Cancer Center, also in Vienna.
Dr. Marcela delCarmen, session comoderator and a gynecologic oncologist at the Massachusetts General Hospital in Boston, asked, “You’ve presented data on the efficacy of the vaccine in the study population, but do you have any data on the effectiveness or the impact that the vaccine will have on the public health atmosphere of the general population?”
“First of all, we saw that the vaccine was doing exactly what was expected. These vaccines don’t have any therapeutic effect, so those women who have been infected at the time of vaccination, we did not observe a benefit during the course of the study. But from the previous study of the quadrivalent vaccine, we know [that] over the course of time, they also will get some benefit,” Dr. Joura replied.
“The second thing is, the vaccine really has the potential with this high effectiveness to change the screening practice in the long term. But what’s definitely needed is good coverage. And in many countries and also in this country, the coverage rates are far from optimal. Once you achieve a rate like in Australia or the United Kingdom, then the next step definitely is a change of screening algorithm,” such as a switch to primary HPV screening, he added.
There is a persistent medical need to develop new HPV vaccines, even though two highly effective vaccines have been on the market for some time, Dr. Joura maintained. “With HPV 16 and 18, you cover about 70% of invasive cervical cancer and about 50% of cervical precancer. Adding the next five most common most oncogenic HPV strains would give a coverage of 90% for both invasive and precancer, giving an additional benefit of 20% for invasive cancer and 35% for cervical precancer,” he elaborated.
In the Merck-sponsored phase IIb/III trial, the investigators randomized 14,215 women aged 16-26 to double-blind receipt of the quadrivalent vaccine (Gardasil, which covers viral types 6, 11, 16, and 18) or the 9-valent vaccine (Gardasil 9, which additionally covers viral types 31, 33, 45, 52, and 58). “It was not possible to have this trial placebo-controlled since two effective vaccines were available, so the controls were vaccinated with the quadrivalent HPV vaccine,” Dr. Joura explained. The women had follow-up with sample collection for up to 54 months.
Initial results showed that antibody titers for the original four viral types in the group given the 9-valent vaccine were noninferior to those in the group given the quadrivalent vaccine, and when compared against the historical placebo arm of the quadrivalent vaccine trial, there was dramatic and near full protection against type 16- and 18-related cervical, vaginal, and vulvar neoplasia. These findings led to approval of the vaccine late last year and a recent publication (N. Engl. J. Med. 2015;372:711-23).
The new, end-of-study data, capturing roughly an additional year of observation, showed that relative to the quadrivalent vaccine, the 9-valent vaccine provided good protection for the five new viral types among women negative for these types at baseline: Efficacy was 97.7% for protection against any neoplasia of the cervix, vagina, or vulva; 97.4% for protection against high-grade neoplasia; and 96.0% for protection against 6-month persistent infection.
“What is important for public health decisions is what is the effect on procedures and treatments,” Dr. Joura said. In fact, the 9-valent vaccine was highly efficacious for reducing external genital biopsies (92.3% risk reduction), cervical biopsy (97.7%), and loop electrosurgical excision procedure/conization (90.2%) related to the five new viral types covered.
The rate of vaccine-related adverse events was 92.2% with the 9-valent vaccine and 87.6% with the quadrivalent vaccine, with the difference mainly due to more injection site reactions with the former. There was two vaccine-related serious adverse events in the 9-valent group and one in the quadrivalent group.
Prevalence data will help assess trends, tailor screening
In a related study, investigators led by Dr. Warner K. Huh, a professor in the department of obstetrics and gynecology at the University of Alabama at Birmingham, determined the relative prevalence of HPV genotypes in the U.S. population.
“We are going to see a transition from the quadrivalent vaccine to the 9-valent vaccine, so information regarding genotypes in this country becomes extremely important,” he said. “There is very limited information in terms of the HPV prevalence for genotypes across the U.S. and more importantly, we almost have zero information on what that prevalence is in a low-risk population. To understand changes in the prevalence in this country, particularly with vaccination and then ultimately as it relates to screening, you are going to need to understand what that baseline data is.”
The investigators analyzed data from 46,751 women aged 21 years or older in the ATHENA study (Evaluation of the Cobas 4800 HPV Test for the Detection of High-Grade Cervical Disease), the largest HPV screening cohort nationally. The Roche-funded study was used to gain Food and Drug Administration approval for primary HPV screening in the United States. Less than 3% of enrolled women had received an HPV vaccine.
The women had HPV testing, in addition to liquid-based Pap testing and colposcopy, with follow-up out to 3 years in a subset. Genotyping was used to detect 16 high-risk types of HPV (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82), and the prevalence of each was benchmarked to that of HPV 16.
“We benchmarked to HPV 16 for a couple of reasons,” Dr. Huh explained. “One of which is that we now have two vaccines – the quadrivalent and the 9-valent vaccines – and we thought it would be interesting to see what happens to that ratio as we have had one for essentially 10 years and the other one transitions in. The other reason, of course, is that it’s a highly prevalent type and a type that’s seen in both vaccines.”
Results showed that the absolute prevalence of all 16 types combined was 11.5% in the entire cohort and 10.0% in the low-risk subset with normal Pap results. In age-stratified analyses, it was higher among women aged 21-24 years than among older women.
The prevalence ratio relative to HPV 16 for the most common viral types among those assessed ranged from 0.12 for HPV 33 to 0.57 for HPV 52.
“The ratios may not be relevant to you today, but they may become highly relevant 10, 20, or 30 years from now,” Dr. Huh commented, discussing HPV type 31, which had a ratio of 0.43, as an example. As coverage by the quadrivalent vaccine and hence protection against type 16 rises, “what we would expect over the next 10 years is that ratio to increase substantially, some theorize as much as fourfold. Then as you roll out the 9-valent vaccine, theoretically, that ratio should normalize back to 0.43, assuming again that the efficacy is equivalent for [type 31] and for type 16,” he explained. “So this is where it becomes very interesting, because if it doesn’t, there is something else going on in the population.”
The new data additionally allow good ability to track the phenomenon of viral type replacement, Dr. Huh said.
“But most importantly, what it allows us to do is to look at screening and the impact of the nonavalent vaccine on screening in the United States. If you all buy into primary HPV screening, the current algorithm uses type 16 and type 18. Well, if type 16 and type 18 go away and these ratios change, then we need to seriously revisit how we do primary HPV screening because the current algorithm is probably not the right algorithm to use,” he maintained.
CHICAGO – The 9-valent human papillomavirus (HPV) vaccine recently approved by the Food and Drug Administration has high efficacy for preventing disease caused by the vaccine-covered viral types and is well tolerated, according to end-of study data from a randomized trial.
The vaccine was on par with the quadrivalent vaccine when it came to protection against infection with the four original viral types covered by both vaccines. Additionally, for the five new viral types, it was associated with a 97% reduction in all cervical, vaginal, and vulvar intraepithelial neoplasia, a 100% reduction in cervical intraepithelial neoplasia 3, and a more than 90% reduction in related procedures and treatments, investigators reported at the Annual meeting of Society of Gynecologic Oncology. Meanwhile, it had a good safety profile.
“The consistency of the data is very reassuring,” said Dr. Elmar A. Joura of the Medical University of Vienna, General Hospital, and Comprehensive Cancer Center, also in Vienna.
Dr. Marcela delCarmen, session comoderator and a gynecologic oncologist at the Massachusetts General Hospital in Boston, asked, “You’ve presented data on the efficacy of the vaccine in the study population, but do you have any data on the effectiveness or the impact that the vaccine will have on the public health atmosphere of the general population?”
“First of all, we saw that the vaccine was doing exactly what was expected. These vaccines don’t have any therapeutic effect, so those women who have been infected at the time of vaccination, we did not observe a benefit during the course of the study. But from the previous study of the quadrivalent vaccine, we know [that] over the course of time, they also will get some benefit,” Dr. Joura replied.
“The second thing is, the vaccine really has the potential with this high effectiveness to change the screening practice in the long term. But what’s definitely needed is good coverage. And in many countries and also in this country, the coverage rates are far from optimal. Once you achieve a rate like in Australia or the United Kingdom, then the next step definitely is a change of screening algorithm,” such as a switch to primary HPV screening, he added.
There is a persistent medical need to develop new HPV vaccines, even though two highly effective vaccines have been on the market for some time, Dr. Joura maintained. “With HPV 16 and 18, you cover about 70% of invasive cervical cancer and about 50% of cervical precancer. Adding the next five most common most oncogenic HPV strains would give a coverage of 90% for both invasive and precancer, giving an additional benefit of 20% for invasive cancer and 35% for cervical precancer,” he elaborated.
In the Merck-sponsored phase IIb/III trial, the investigators randomized 14,215 women aged 16-26 to double-blind receipt of the quadrivalent vaccine (Gardasil, which covers viral types 6, 11, 16, and 18) or the 9-valent vaccine (Gardasil 9, which additionally covers viral types 31, 33, 45, 52, and 58). “It was not possible to have this trial placebo-controlled since two effective vaccines were available, so the controls were vaccinated with the quadrivalent HPV vaccine,” Dr. Joura explained. The women had follow-up with sample collection for up to 54 months.
Initial results showed that antibody titers for the original four viral types in the group given the 9-valent vaccine were noninferior to those in the group given the quadrivalent vaccine, and when compared against the historical placebo arm of the quadrivalent vaccine trial, there was dramatic and near full protection against type 16- and 18-related cervical, vaginal, and vulvar neoplasia. These findings led to approval of the vaccine late last year and a recent publication (N. Engl. J. Med. 2015;372:711-23).
The new, end-of-study data, capturing roughly an additional year of observation, showed that relative to the quadrivalent vaccine, the 9-valent vaccine provided good protection for the five new viral types among women negative for these types at baseline: Efficacy was 97.7% for protection against any neoplasia of the cervix, vagina, or vulva; 97.4% for protection against high-grade neoplasia; and 96.0% for protection against 6-month persistent infection.
“What is important for public health decisions is what is the effect on procedures and treatments,” Dr. Joura said. In fact, the 9-valent vaccine was highly efficacious for reducing external genital biopsies (92.3% risk reduction), cervical biopsy (97.7%), and loop electrosurgical excision procedure/conization (90.2%) related to the five new viral types covered.
The rate of vaccine-related adverse events was 92.2% with the 9-valent vaccine and 87.6% with the quadrivalent vaccine, with the difference mainly due to more injection site reactions with the former. There was two vaccine-related serious adverse events in the 9-valent group and one in the quadrivalent group.
Prevalence data will help assess trends, tailor screening
In a related study, investigators led by Dr. Warner K. Huh, a professor in the department of obstetrics and gynecology at the University of Alabama at Birmingham, determined the relative prevalence of HPV genotypes in the U.S. population.
“We are going to see a transition from the quadrivalent vaccine to the 9-valent vaccine, so information regarding genotypes in this country becomes extremely important,” he said. “There is very limited information in terms of the HPV prevalence for genotypes across the U.S. and more importantly, we almost have zero information on what that prevalence is in a low-risk population. To understand changes in the prevalence in this country, particularly with vaccination and then ultimately as it relates to screening, you are going to need to understand what that baseline data is.”
The investigators analyzed data from 46,751 women aged 21 years or older in the ATHENA study (Evaluation of the Cobas 4800 HPV Test for the Detection of High-Grade Cervical Disease), the largest HPV screening cohort nationally. The Roche-funded study was used to gain Food and Drug Administration approval for primary HPV screening in the United States. Less than 3% of enrolled women had received an HPV vaccine.
The women had HPV testing, in addition to liquid-based Pap testing and colposcopy, with follow-up out to 3 years in a subset. Genotyping was used to detect 16 high-risk types of HPV (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82), and the prevalence of each was benchmarked to that of HPV 16.
“We benchmarked to HPV 16 for a couple of reasons,” Dr. Huh explained. “One of which is that we now have two vaccines – the quadrivalent and the 9-valent vaccines – and we thought it would be interesting to see what happens to that ratio as we have had one for essentially 10 years and the other one transitions in. The other reason, of course, is that it’s a highly prevalent type and a type that’s seen in both vaccines.”
Results showed that the absolute prevalence of all 16 types combined was 11.5% in the entire cohort and 10.0% in the low-risk subset with normal Pap results. In age-stratified analyses, it was higher among women aged 21-24 years than among older women.
The prevalence ratio relative to HPV 16 for the most common viral types among those assessed ranged from 0.12 for HPV 33 to 0.57 for HPV 52.
“The ratios may not be relevant to you today, but they may become highly relevant 10, 20, or 30 years from now,” Dr. Huh commented, discussing HPV type 31, which had a ratio of 0.43, as an example. As coverage by the quadrivalent vaccine and hence protection against type 16 rises, “what we would expect over the next 10 years is that ratio to increase substantially, some theorize as much as fourfold. Then as you roll out the 9-valent vaccine, theoretically, that ratio should normalize back to 0.43, assuming again that the efficacy is equivalent for [type 31] and for type 16,” he explained. “So this is where it becomes very interesting, because if it doesn’t, there is something else going on in the population.”
The new data additionally allow good ability to track the phenomenon of viral type replacement, Dr. Huh said.
“But most importantly, what it allows us to do is to look at screening and the impact of the nonavalent vaccine on screening in the United States. If you all buy into primary HPV screening, the current algorithm uses type 16 and type 18. Well, if type 16 and type 18 go away and these ratios change, then we need to seriously revisit how we do primary HPV screening because the current algorithm is probably not the right algorithm to use,” he maintained.
CHICAGO – The 9-valent human papillomavirus (HPV) vaccine recently approved by the Food and Drug Administration has high efficacy for preventing disease caused by the vaccine-covered viral types and is well tolerated, according to end-of study data from a randomized trial.
The vaccine was on par with the quadrivalent vaccine when it came to protection against infection with the four original viral types covered by both vaccines. Additionally, for the five new viral types, it was associated with a 97% reduction in all cervical, vaginal, and vulvar intraepithelial neoplasia, a 100% reduction in cervical intraepithelial neoplasia 3, and a more than 90% reduction in related procedures and treatments, investigators reported at the Annual meeting of Society of Gynecologic Oncology. Meanwhile, it had a good safety profile.
“The consistency of the data is very reassuring,” said Dr. Elmar A. Joura of the Medical University of Vienna, General Hospital, and Comprehensive Cancer Center, also in Vienna.
Dr. Marcela delCarmen, session comoderator and a gynecologic oncologist at the Massachusetts General Hospital in Boston, asked, “You’ve presented data on the efficacy of the vaccine in the study population, but do you have any data on the effectiveness or the impact that the vaccine will have on the public health atmosphere of the general population?”
“First of all, we saw that the vaccine was doing exactly what was expected. These vaccines don’t have any therapeutic effect, so those women who have been infected at the time of vaccination, we did not observe a benefit during the course of the study. But from the previous study of the quadrivalent vaccine, we know [that] over the course of time, they also will get some benefit,” Dr. Joura replied.
“The second thing is, the vaccine really has the potential with this high effectiveness to change the screening practice in the long term. But what’s definitely needed is good coverage. And in many countries and also in this country, the coverage rates are far from optimal. Once you achieve a rate like in Australia or the United Kingdom, then the next step definitely is a change of screening algorithm,” such as a switch to primary HPV screening, he added.
There is a persistent medical need to develop new HPV vaccines, even though two highly effective vaccines have been on the market for some time, Dr. Joura maintained. “With HPV 16 and 18, you cover about 70% of invasive cervical cancer and about 50% of cervical precancer. Adding the next five most common most oncogenic HPV strains would give a coverage of 90% for both invasive and precancer, giving an additional benefit of 20% for invasive cancer and 35% for cervical precancer,” he elaborated.
In the Merck-sponsored phase IIb/III trial, the investigators randomized 14,215 women aged 16-26 to double-blind receipt of the quadrivalent vaccine (Gardasil, which covers viral types 6, 11, 16, and 18) or the 9-valent vaccine (Gardasil 9, which additionally covers viral types 31, 33, 45, 52, and 58). “It was not possible to have this trial placebo-controlled since two effective vaccines were available, so the controls were vaccinated with the quadrivalent HPV vaccine,” Dr. Joura explained. The women had follow-up with sample collection for up to 54 months.
Initial results showed that antibody titers for the original four viral types in the group given the 9-valent vaccine were noninferior to those in the group given the quadrivalent vaccine, and when compared against the historical placebo arm of the quadrivalent vaccine trial, there was dramatic and near full protection against type 16- and 18-related cervical, vaginal, and vulvar neoplasia. These findings led to approval of the vaccine late last year and a recent publication (N. Engl. J. Med. 2015;372:711-23).
The new, end-of-study data, capturing roughly an additional year of observation, showed that relative to the quadrivalent vaccine, the 9-valent vaccine provided good protection for the five new viral types among women negative for these types at baseline: Efficacy was 97.7% for protection against any neoplasia of the cervix, vagina, or vulva; 97.4% for protection against high-grade neoplasia; and 96.0% for protection against 6-month persistent infection.
“What is important for public health decisions is what is the effect on procedures and treatments,” Dr. Joura said. In fact, the 9-valent vaccine was highly efficacious for reducing external genital biopsies (92.3% risk reduction), cervical biopsy (97.7%), and loop electrosurgical excision procedure/conization (90.2%) related to the five new viral types covered.
The rate of vaccine-related adverse events was 92.2% with the 9-valent vaccine and 87.6% with the quadrivalent vaccine, with the difference mainly due to more injection site reactions with the former. There was two vaccine-related serious adverse events in the 9-valent group and one in the quadrivalent group.
Prevalence data will help assess trends, tailor screening
In a related study, investigators led by Dr. Warner K. Huh, a professor in the department of obstetrics and gynecology at the University of Alabama at Birmingham, determined the relative prevalence of HPV genotypes in the U.S. population.
“We are going to see a transition from the quadrivalent vaccine to the 9-valent vaccine, so information regarding genotypes in this country becomes extremely important,” he said. “There is very limited information in terms of the HPV prevalence for genotypes across the U.S. and more importantly, we almost have zero information on what that prevalence is in a low-risk population. To understand changes in the prevalence in this country, particularly with vaccination and then ultimately as it relates to screening, you are going to need to understand what that baseline data is.”
The investigators analyzed data from 46,751 women aged 21 years or older in the ATHENA study (Evaluation of the Cobas 4800 HPV Test for the Detection of High-Grade Cervical Disease), the largest HPV screening cohort nationally. The Roche-funded study was used to gain Food and Drug Administration approval for primary HPV screening in the United States. Less than 3% of enrolled women had received an HPV vaccine.
The women had HPV testing, in addition to liquid-based Pap testing and colposcopy, with follow-up out to 3 years in a subset. Genotyping was used to detect 16 high-risk types of HPV (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82), and the prevalence of each was benchmarked to that of HPV 16.
“We benchmarked to HPV 16 for a couple of reasons,” Dr. Huh explained. “One of which is that we now have two vaccines – the quadrivalent and the 9-valent vaccines – and we thought it would be interesting to see what happens to that ratio as we have had one for essentially 10 years and the other one transitions in. The other reason, of course, is that it’s a highly prevalent type and a type that’s seen in both vaccines.”
Results showed that the absolute prevalence of all 16 types combined was 11.5% in the entire cohort and 10.0% in the low-risk subset with normal Pap results. In age-stratified analyses, it was higher among women aged 21-24 years than among older women.
The prevalence ratio relative to HPV 16 for the most common viral types among those assessed ranged from 0.12 for HPV 33 to 0.57 for HPV 52.
“The ratios may not be relevant to you today, but they may become highly relevant 10, 20, or 30 years from now,” Dr. Huh commented, discussing HPV type 31, which had a ratio of 0.43, as an example. As coverage by the quadrivalent vaccine and hence protection against type 16 rises, “what we would expect over the next 10 years is that ratio to increase substantially, some theorize as much as fourfold. Then as you roll out the 9-valent vaccine, theoretically, that ratio should normalize back to 0.43, assuming again that the efficacy is equivalent for [type 31] and for type 16,” he explained. “So this is where it becomes very interesting, because if it doesn’t, there is something else going on in the population.”
The new data additionally allow good ability to track the phenomenon of viral type replacement, Dr. Huh said.
“But most importantly, what it allows us to do is to look at screening and the impact of the nonavalent vaccine on screening in the United States. If you all buy into primary HPV screening, the current algorithm uses type 16 and type 18. Well, if type 16 and type 18 go away and these ratios change, then we need to seriously revisit how we do primary HPV screening because the current algorithm is probably not the right algorithm to use,” he maintained.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: The 9-valent vaccine has broader coverage than does the quadrivalent vaccine and is similarly safe.
Major finding: The 9-valent vaccine had 97% efficacy against disease related to the five newly covered viral types.
Data source: A randomized, double-blind, phase IIb/III trial among 14,215 women aged 16 to 26.
Disclosures: Dr. Joura disclosed that he is an investigator for Merck HPV vaccines and with GlaxoSmithKline epidemiologic trials, and lectures for Merck, Sanofi Pasteur MSD, GlaxoSmithKline, and Roche; the trial was sponsored by Merck. Dr. Huh disclosed that he is a nonpaid consultant for Roche Molecular Systems and a Scientific Advisory Board member for Merck’s Gardasil 9 program; the study was funded by Roche.
Bevacizumab confers survival benefit in platinum-sensitive ovarian cancer
CHICAGO – Adding the anti-angiogenic agent bevacizumab to chemotherapy improves outcomes in women with platinum-sensitive recurrent epithelial ovarian cancer, the randomized Gynecologic Oncology Group 213 trial has shown.
Results reported at the annual meeting of the Society of Gynecologic Oncology showed that addition of bevacizumab reduced the risk of death (one of the trial’s co-primary endpoints) by a near-significant 17%, which amounted to 4.9 more months of life.
“Paclitaxel, carboplatin, and bevacizumab extended overall survival in patients with platinum-sensitive recurrent ovarian cancer, but narrowly missed that statistical upper limit of significance. The combination was associated with a significant improvement in progression-free survival as well as objective response,” commented lead investigator Dr. Robert L. Coleman, professor and vice chair of clinical research in the department of gynecologic oncology and reproductive medicine, University of Texas MD Anderson Cancer Center in Houston.
“Although toxicity was more commonly observed on the concomitant bevacizumab arm, no new safety signals were detected, and no negative impact on a patient-reported global functioning scale was observed,” he added.
Session attendee Dr. Brad Monk of the University of Arizona Cancer Center in Phoenix wondered if the overall survival results could be interpreted as positive in light of information gleaned since the trial’s inception.
“I think we all accept that 5 months is 5 months of overall survival. I accepted 8 years ago, when the study was developed, that [the statistical test used] was a two-sided test, looking for both superiority and inferiority,” he said. “But today we would never expect that bevacizumab would make survival worse. So if you were to apply a one-tailed test, the P value would go from .056 to .028, and then you would say it’s positive. I know that we can’t change the statistical design, but is this study really negative statistically? Is this a practice-changing study?”
“You are right, we have learned a lot,” Dr. Coleman agreed. “I think one of the most striking differences in this trial versus what our expectations were was the performance of the control arm,” wherein survival far exceeded the 22 months assumed in the trial’s planning; meanwhile, a progression-free survival benefit of bevacizumab was preserved. “I think that this is the strongest signal for that, and the fact that we were able to achieve that knowing that the environment has changed so much, to me, does feel like it is practice changing,” he said.
Two previous trials — CALYPSO (Caelyx Plus Carboplatin Versus Paclitaxel Plus Carboplatin in Patients With Epithelial Ovarian Cancer in Late Relapse) and OCEANS (Ovarian Cancer Study Comparing Efficacy and Safety of Chemotherapy and Anti-Angiogenic Therapy in Platinum-Sensitive Recurrent Disease) — tested variations on a chemotherapy backbone exclusively among platinum-sensitive patients, he noted, giving some background to the research. Neither found a significant survival benefit (Br J Cancer. 2012;107:588-91 and J Clin Oncol. 2012;30:2039-45).
Participants in the current trial were 674 women with ovarian cancer from the United States, Japan, and South Korea who had a complete response to primary therapy but experienced a recurrence at least 6 months later. They were randomized twice: first to receive secondary cytoreductive surgery or not, and then to receive carboplatin plus paclitaxel, with versus without concurrent and maintenance bevacizumab (Avastin). Genentech provided the agent and supported the National Cancer Institute/Cancer Therapy Evaluation Program for the trial.
In terms of adverse events of special interest, the bevacizumab group had significantly higher rates of grade 3 or worse thromboembolism (4% vs. 1%), infection (13% vs. 6%), hypertension (12% vs. less than 1%), proteinuria (8% vs. 0%), and joint pain (15% vs. 5%), reported Dr. Coleman, who disclosed that he had no conflicts of interest.
“However, arterial thrombosis, neutropenia, and febrile neutropenia were not different between the two arms. And in addition, while gastrointestinal events were more common in the experimental arm, the grade 3/4 events were no different, and no patient died as a result of this adverse event, “ he noted. Furthermore, the allergy (mainly carboplatin hypersensitivity) and grade 3 or worse neuropathy were essentially equally common across groups.
Median overall survival was 42.2 months with bevacizumab and 37.3 months without it (hazard ratio 0.83; P = .056). In subgroup analyses, benefit was similar of whether patients had undergone randomization for cytoreductive surgery, had a progression-free interval of more than 12 months, and had received bevacizumab before.
Progression-free survival was 13.8 months with bevacizumab and 10.4 months without it, a significant difference (hazard ratio 0.61; P less than .0001). The overall response rate was also better with the anti-angiogenic agent (79% vs. 59%, P less than .0001).
Patient-reported quality of life did not differ significantly between the two treatment groups, according to Dr. Coleman. Not surprisingly, those given bevacizumab were less likely to receive more of that agent or another anti-angiogenic agent as the next line of therapy after progression.
Data for the second co-primary endpoint, the overall survival impact of secondary cytoreductive surgery, are currently pending, he said.
CHICAGO – Adding the anti-angiogenic agent bevacizumab to chemotherapy improves outcomes in women with platinum-sensitive recurrent epithelial ovarian cancer, the randomized Gynecologic Oncology Group 213 trial has shown.
Results reported at the annual meeting of the Society of Gynecologic Oncology showed that addition of bevacizumab reduced the risk of death (one of the trial’s co-primary endpoints) by a near-significant 17%, which amounted to 4.9 more months of life.
“Paclitaxel, carboplatin, and bevacizumab extended overall survival in patients with platinum-sensitive recurrent ovarian cancer, but narrowly missed that statistical upper limit of significance. The combination was associated with a significant improvement in progression-free survival as well as objective response,” commented lead investigator Dr. Robert L. Coleman, professor and vice chair of clinical research in the department of gynecologic oncology and reproductive medicine, University of Texas MD Anderson Cancer Center in Houston.
“Although toxicity was more commonly observed on the concomitant bevacizumab arm, no new safety signals were detected, and no negative impact on a patient-reported global functioning scale was observed,” he added.
Session attendee Dr. Brad Monk of the University of Arizona Cancer Center in Phoenix wondered if the overall survival results could be interpreted as positive in light of information gleaned since the trial’s inception.
“I think we all accept that 5 months is 5 months of overall survival. I accepted 8 years ago, when the study was developed, that [the statistical test used] was a two-sided test, looking for both superiority and inferiority,” he said. “But today we would never expect that bevacizumab would make survival worse. So if you were to apply a one-tailed test, the P value would go from .056 to .028, and then you would say it’s positive. I know that we can’t change the statistical design, but is this study really negative statistically? Is this a practice-changing study?”
“You are right, we have learned a lot,” Dr. Coleman agreed. “I think one of the most striking differences in this trial versus what our expectations were was the performance of the control arm,” wherein survival far exceeded the 22 months assumed in the trial’s planning; meanwhile, a progression-free survival benefit of bevacizumab was preserved. “I think that this is the strongest signal for that, and the fact that we were able to achieve that knowing that the environment has changed so much, to me, does feel like it is practice changing,” he said.
Two previous trials — CALYPSO (Caelyx Plus Carboplatin Versus Paclitaxel Plus Carboplatin in Patients With Epithelial Ovarian Cancer in Late Relapse) and OCEANS (Ovarian Cancer Study Comparing Efficacy and Safety of Chemotherapy and Anti-Angiogenic Therapy in Platinum-Sensitive Recurrent Disease) — tested variations on a chemotherapy backbone exclusively among platinum-sensitive patients, he noted, giving some background to the research. Neither found a significant survival benefit (Br J Cancer. 2012;107:588-91 and J Clin Oncol. 2012;30:2039-45).
Participants in the current trial were 674 women with ovarian cancer from the United States, Japan, and South Korea who had a complete response to primary therapy but experienced a recurrence at least 6 months later. They were randomized twice: first to receive secondary cytoreductive surgery or not, and then to receive carboplatin plus paclitaxel, with versus without concurrent and maintenance bevacizumab (Avastin). Genentech provided the agent and supported the National Cancer Institute/Cancer Therapy Evaluation Program for the trial.
In terms of adverse events of special interest, the bevacizumab group had significantly higher rates of grade 3 or worse thromboembolism (4% vs. 1%), infection (13% vs. 6%), hypertension (12% vs. less than 1%), proteinuria (8% vs. 0%), and joint pain (15% vs. 5%), reported Dr. Coleman, who disclosed that he had no conflicts of interest.
“However, arterial thrombosis, neutropenia, and febrile neutropenia were not different between the two arms. And in addition, while gastrointestinal events were more common in the experimental arm, the grade 3/4 events were no different, and no patient died as a result of this adverse event, “ he noted. Furthermore, the allergy (mainly carboplatin hypersensitivity) and grade 3 or worse neuropathy were essentially equally common across groups.
Median overall survival was 42.2 months with bevacizumab and 37.3 months without it (hazard ratio 0.83; P = .056). In subgroup analyses, benefit was similar of whether patients had undergone randomization for cytoreductive surgery, had a progression-free interval of more than 12 months, and had received bevacizumab before.
Progression-free survival was 13.8 months with bevacizumab and 10.4 months without it, a significant difference (hazard ratio 0.61; P less than .0001). The overall response rate was also better with the anti-angiogenic agent (79% vs. 59%, P less than .0001).
Patient-reported quality of life did not differ significantly between the two treatment groups, according to Dr. Coleman. Not surprisingly, those given bevacizumab were less likely to receive more of that agent or another anti-angiogenic agent as the next line of therapy after progression.
Data for the second co-primary endpoint, the overall survival impact of secondary cytoreductive surgery, are currently pending, he said.
CHICAGO – Adding the anti-angiogenic agent bevacizumab to chemotherapy improves outcomes in women with platinum-sensitive recurrent epithelial ovarian cancer, the randomized Gynecologic Oncology Group 213 trial has shown.
Results reported at the annual meeting of the Society of Gynecologic Oncology showed that addition of bevacizumab reduced the risk of death (one of the trial’s co-primary endpoints) by a near-significant 17%, which amounted to 4.9 more months of life.
“Paclitaxel, carboplatin, and bevacizumab extended overall survival in patients with platinum-sensitive recurrent ovarian cancer, but narrowly missed that statistical upper limit of significance. The combination was associated with a significant improvement in progression-free survival as well as objective response,” commented lead investigator Dr. Robert L. Coleman, professor and vice chair of clinical research in the department of gynecologic oncology and reproductive medicine, University of Texas MD Anderson Cancer Center in Houston.
“Although toxicity was more commonly observed on the concomitant bevacizumab arm, no new safety signals were detected, and no negative impact on a patient-reported global functioning scale was observed,” he added.
Session attendee Dr. Brad Monk of the University of Arizona Cancer Center in Phoenix wondered if the overall survival results could be interpreted as positive in light of information gleaned since the trial’s inception.
“I think we all accept that 5 months is 5 months of overall survival. I accepted 8 years ago, when the study was developed, that [the statistical test used] was a two-sided test, looking for both superiority and inferiority,” he said. “But today we would never expect that bevacizumab would make survival worse. So if you were to apply a one-tailed test, the P value would go from .056 to .028, and then you would say it’s positive. I know that we can’t change the statistical design, but is this study really negative statistically? Is this a practice-changing study?”
“You are right, we have learned a lot,” Dr. Coleman agreed. “I think one of the most striking differences in this trial versus what our expectations were was the performance of the control arm,” wherein survival far exceeded the 22 months assumed in the trial’s planning; meanwhile, a progression-free survival benefit of bevacizumab was preserved. “I think that this is the strongest signal for that, and the fact that we were able to achieve that knowing that the environment has changed so much, to me, does feel like it is practice changing,” he said.
Two previous trials — CALYPSO (Caelyx Plus Carboplatin Versus Paclitaxel Plus Carboplatin in Patients With Epithelial Ovarian Cancer in Late Relapse) and OCEANS (Ovarian Cancer Study Comparing Efficacy and Safety of Chemotherapy and Anti-Angiogenic Therapy in Platinum-Sensitive Recurrent Disease) — tested variations on a chemotherapy backbone exclusively among platinum-sensitive patients, he noted, giving some background to the research. Neither found a significant survival benefit (Br J Cancer. 2012;107:588-91 and J Clin Oncol. 2012;30:2039-45).
Participants in the current trial were 674 women with ovarian cancer from the United States, Japan, and South Korea who had a complete response to primary therapy but experienced a recurrence at least 6 months later. They were randomized twice: first to receive secondary cytoreductive surgery or not, and then to receive carboplatin plus paclitaxel, with versus without concurrent and maintenance bevacizumab (Avastin). Genentech provided the agent and supported the National Cancer Institute/Cancer Therapy Evaluation Program for the trial.
In terms of adverse events of special interest, the bevacizumab group had significantly higher rates of grade 3 or worse thromboembolism (4% vs. 1%), infection (13% vs. 6%), hypertension (12% vs. less than 1%), proteinuria (8% vs. 0%), and joint pain (15% vs. 5%), reported Dr. Coleman, who disclosed that he had no conflicts of interest.
“However, arterial thrombosis, neutropenia, and febrile neutropenia were not different between the two arms. And in addition, while gastrointestinal events were more common in the experimental arm, the grade 3/4 events were no different, and no patient died as a result of this adverse event, “ he noted. Furthermore, the allergy (mainly carboplatin hypersensitivity) and grade 3 or worse neuropathy were essentially equally common across groups.
Median overall survival was 42.2 months with bevacizumab and 37.3 months without it (hazard ratio 0.83; P = .056). In subgroup analyses, benefit was similar of whether patients had undergone randomization for cytoreductive surgery, had a progression-free interval of more than 12 months, and had received bevacizumab before.
Progression-free survival was 13.8 months with bevacizumab and 10.4 months without it, a significant difference (hazard ratio 0.61; P less than .0001). The overall response rate was also better with the anti-angiogenic agent (79% vs. 59%, P less than .0001).
Patient-reported quality of life did not differ significantly between the two treatment groups, according to Dr. Coleman. Not surprisingly, those given bevacizumab were less likely to receive more of that agent or another anti-angiogenic agent as the next line of therapy after progression.
Data for the second co-primary endpoint, the overall survival impact of secondary cytoreductive surgery, are currently pending, he said.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: Addition of bevacizumab to chemotherapy yielded a near-significant 4.9-month gain in overall survival.
Major finding: Patients given bevacizumab had a reduced risk of death relative to peers given chemotherapy alone (hazard ratio 0.83; P = .056).
Data source: A randomized phase 3 trial in 674 women with platinum-sensitive recurrent ovarian cancer.
Disclosures: Dr. Coleman disclosed that he had no conflicts of interest. Genentech provided the bevacizumab and supported the National Cancer Institute/Cancer Therapy Evaluation Program for the trial.
SCORPION: Interval debulking is safer in advanced ovarian cancer
CHICAGO – Delaying debulking until patients have had some chemotherapy is a safer strategy for women with advanced ovarian cancer, according to interim results of the randomized phase III SCORPION trial (Surgical Complications Related to Primary or Interval Debulking in Ovarian Neoplasm).
The odds of complications such as sepsis, organ failure, and death in the perioperative period were 19.3 times higher among women who underwent primary debulking than among counterparts who underwent neoadjuvant chemotherapy followed by interval debulking, Dr. Anna Fagotti reported at the annual meeting of the Society of Gynecologic Oncology.
“Primary debulking surgery is associated with a statistically significantly higher risk of major perioperative morbidity with respect to interval debulking surgery in high–tumor load advanced epithelial ovarian cancer patients,” she said.
“Most of these complications, however, are grade 3, with a higher incidence than reported from retrospective analyses in the literature. The reported mortality rate [with primary debulking] … is in line with the literature data,” added Dr. Fagotti of the University of Perugia, Terni, Italy. “Our survival data will definitely clarify whether such a severe complication rate is acceptable in terms of cost-effectiveness.”
The trial also offers a cautionary note about study methodology in this setting, she said. Specifically, “any neoadjuvant chemotherapy clinical study that is based on instrumental or clinical evaluation only, excluding staging laparoscopy, might include very heterogeneous populations, thus leading to substantial biases.”
Giving some background to the research, Dr. Fagotti noted that case series have shown a survival advantage for women with advanced ovarian cancer who undergo primary debulking with optimal or no residual tumor, albeit at the cost of more extensive surgery. But randomized trials have shown similar survival and fewer complications with the interval debulking approach.
“We know also that many limits can be ascribed to these studies, so, as a consequence, there are gray-zone patients in whom the best primary treatment option is not clear yet,” she commented.
The 110 patients studied in SCORPION had suspected advanced ovarian cancer with a FIGO (International Federation of Gynecology and Obstetrics) stage of IIIc or IV, and had an intraoperative staging laparoscopy score of 8-12. They were randomized evenly to primary debulking followed by adjuvant chemotherapy or to neoadjuvant chemotherapy followed by interval debulking.
Three patients in the latter arm had progression during their chemotherapy and were therefore unable to proceed to their planned surgery, Dr. Fagotti reported.
On average, women in the interval debulking group had less extensive surgery than peers in the primary debulking group. In particular, they were significantly less likely to undergo pelvic and/or abdominal peritonectomy (58% vs. 100%), bowel resection (19% vs. 100%), diaphragmatic peritonectomy or resection (38% vs. 100%), partial hepatectomy (0% vs. 18%), and splenectomy (4% vs. 53%). Overall, they were nearly half as likely to have any upper abdominal procedure (58% vs. 100%).
Ninety percent of all patients had optimal cytoreduction to residual disease of 1 cm or less, with no significant difference between groups, Dr. Fagotti said.
In terms of surgical measures, the interval debulking group had a median operative time that was about a third shorter and median blood loss and hospital stays about half those with primary debulking.
The interval debulking group was significantly less likely to experience any major postoperative complication (6% vs. 53%, P = .001). Notably, they had lower rates of pleural effusion (2% vs. 31%), sepsis (0% vs. 7%), pulmonary thromboembolism (0% vs. 6%), reoperation with organ resection (0% vs. 4%), multiorgan failure (0% vs. 2%), and surgery-related death (0% vs. 4%).
CHICAGO – Delaying debulking until patients have had some chemotherapy is a safer strategy for women with advanced ovarian cancer, according to interim results of the randomized phase III SCORPION trial (Surgical Complications Related to Primary or Interval Debulking in Ovarian Neoplasm).
The odds of complications such as sepsis, organ failure, and death in the perioperative period were 19.3 times higher among women who underwent primary debulking than among counterparts who underwent neoadjuvant chemotherapy followed by interval debulking, Dr. Anna Fagotti reported at the annual meeting of the Society of Gynecologic Oncology.
“Primary debulking surgery is associated with a statistically significantly higher risk of major perioperative morbidity with respect to interval debulking surgery in high–tumor load advanced epithelial ovarian cancer patients,” she said.
“Most of these complications, however, are grade 3, with a higher incidence than reported from retrospective analyses in the literature. The reported mortality rate [with primary debulking] … is in line with the literature data,” added Dr. Fagotti of the University of Perugia, Terni, Italy. “Our survival data will definitely clarify whether such a severe complication rate is acceptable in terms of cost-effectiveness.”
The trial also offers a cautionary note about study methodology in this setting, she said. Specifically, “any neoadjuvant chemotherapy clinical study that is based on instrumental or clinical evaluation only, excluding staging laparoscopy, might include very heterogeneous populations, thus leading to substantial biases.”
Giving some background to the research, Dr. Fagotti noted that case series have shown a survival advantage for women with advanced ovarian cancer who undergo primary debulking with optimal or no residual tumor, albeit at the cost of more extensive surgery. But randomized trials have shown similar survival and fewer complications with the interval debulking approach.
“We know also that many limits can be ascribed to these studies, so, as a consequence, there are gray-zone patients in whom the best primary treatment option is not clear yet,” she commented.
The 110 patients studied in SCORPION had suspected advanced ovarian cancer with a FIGO (International Federation of Gynecology and Obstetrics) stage of IIIc or IV, and had an intraoperative staging laparoscopy score of 8-12. They were randomized evenly to primary debulking followed by adjuvant chemotherapy or to neoadjuvant chemotherapy followed by interval debulking.
Three patients in the latter arm had progression during their chemotherapy and were therefore unable to proceed to their planned surgery, Dr. Fagotti reported.
On average, women in the interval debulking group had less extensive surgery than peers in the primary debulking group. In particular, they were significantly less likely to undergo pelvic and/or abdominal peritonectomy (58% vs. 100%), bowel resection (19% vs. 100%), diaphragmatic peritonectomy or resection (38% vs. 100%), partial hepatectomy (0% vs. 18%), and splenectomy (4% vs. 53%). Overall, they were nearly half as likely to have any upper abdominal procedure (58% vs. 100%).
Ninety percent of all patients had optimal cytoreduction to residual disease of 1 cm or less, with no significant difference between groups, Dr. Fagotti said.
In terms of surgical measures, the interval debulking group had a median operative time that was about a third shorter and median blood loss and hospital stays about half those with primary debulking.
The interval debulking group was significantly less likely to experience any major postoperative complication (6% vs. 53%, P = .001). Notably, they had lower rates of pleural effusion (2% vs. 31%), sepsis (0% vs. 7%), pulmonary thromboembolism (0% vs. 6%), reoperation with organ resection (0% vs. 4%), multiorgan failure (0% vs. 2%), and surgery-related death (0% vs. 4%).
CHICAGO – Delaying debulking until patients have had some chemotherapy is a safer strategy for women with advanced ovarian cancer, according to interim results of the randomized phase III SCORPION trial (Surgical Complications Related to Primary or Interval Debulking in Ovarian Neoplasm).
The odds of complications such as sepsis, organ failure, and death in the perioperative period were 19.3 times higher among women who underwent primary debulking than among counterparts who underwent neoadjuvant chemotherapy followed by interval debulking, Dr. Anna Fagotti reported at the annual meeting of the Society of Gynecologic Oncology.
“Primary debulking surgery is associated with a statistically significantly higher risk of major perioperative morbidity with respect to interval debulking surgery in high–tumor load advanced epithelial ovarian cancer patients,” she said.
“Most of these complications, however, are grade 3, with a higher incidence than reported from retrospective analyses in the literature. The reported mortality rate [with primary debulking] … is in line with the literature data,” added Dr. Fagotti of the University of Perugia, Terni, Italy. “Our survival data will definitely clarify whether such a severe complication rate is acceptable in terms of cost-effectiveness.”
The trial also offers a cautionary note about study methodology in this setting, she said. Specifically, “any neoadjuvant chemotherapy clinical study that is based on instrumental or clinical evaluation only, excluding staging laparoscopy, might include very heterogeneous populations, thus leading to substantial biases.”
Giving some background to the research, Dr. Fagotti noted that case series have shown a survival advantage for women with advanced ovarian cancer who undergo primary debulking with optimal or no residual tumor, albeit at the cost of more extensive surgery. But randomized trials have shown similar survival and fewer complications with the interval debulking approach.
“We know also that many limits can be ascribed to these studies, so, as a consequence, there are gray-zone patients in whom the best primary treatment option is not clear yet,” she commented.
The 110 patients studied in SCORPION had suspected advanced ovarian cancer with a FIGO (International Federation of Gynecology and Obstetrics) stage of IIIc or IV, and had an intraoperative staging laparoscopy score of 8-12. They were randomized evenly to primary debulking followed by adjuvant chemotherapy or to neoadjuvant chemotherapy followed by interval debulking.
Three patients in the latter arm had progression during their chemotherapy and were therefore unable to proceed to their planned surgery, Dr. Fagotti reported.
On average, women in the interval debulking group had less extensive surgery than peers in the primary debulking group. In particular, they were significantly less likely to undergo pelvic and/or abdominal peritonectomy (58% vs. 100%), bowel resection (19% vs. 100%), diaphragmatic peritonectomy or resection (38% vs. 100%), partial hepatectomy (0% vs. 18%), and splenectomy (4% vs. 53%). Overall, they were nearly half as likely to have any upper abdominal procedure (58% vs. 100%).
Ninety percent of all patients had optimal cytoreduction to residual disease of 1 cm or less, with no significant difference between groups, Dr. Fagotti said.
In terms of surgical measures, the interval debulking group had a median operative time that was about a third shorter and median blood loss and hospital stays about half those with primary debulking.
The interval debulking group was significantly less likely to experience any major postoperative complication (6% vs. 53%, P = .001). Notably, they had lower rates of pleural effusion (2% vs. 31%), sepsis (0% vs. 7%), pulmonary thromboembolism (0% vs. 6%), reoperation with organ resection (0% vs. 4%), multiorgan failure (0% vs. 2%), and surgery-related death (0% vs. 4%).
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: Complications were much less common with interval debulking than with primary debulking.
Major finding: The odds of major perioperative morbidity were 19.3 times higher with primary debulking than with neoadjuvant chemotherapy followed by interval debulking.
Data source: Interim results of a randomized phase III trial among 110 patients with ovarian cancer and a high tumor load.
Disclosures: Dr. Fagotti disclosed that she had no relevant conflicts of interest.
QOL independently predicts outcomes in ovarian cancer
CHICAGO– Quality of life at baseline and during treatment is an important prognostic factor in women with ovarian cancer, confirms an analysis reported at the annual meeting of the Society of Gynecologic Oncology.
Patients’ baseline quality of life score was independently associated with both progression-free and overall survival among 1,152 women participating in the Gynecologic Oncology Group (GOG) 218 trial, a randomized phase III trial comparing chemotherapy with versus without bevacizumab (Avastin), reported Dr. Neil T. Phippen of Walter Reed National Military Medical Center, Bethesda, Md.
Quality of life was assessed at six time points with FACT-O TOI (the Functional Assessment of Cancer Therapy–Ovarian Trial Outcome Index), on which possible scores range from 0-104 and higher scores indicate better quality of life. Women were included in analyses if they had completed the questionnaire at two or more time points.
Patients whose FACT-O TOI scores improved during treatment had a 4- to 5-month longer progression-free survival and a 20- to 25-month longer overall survival than counterparts whose scores worsened.
“Coupled with previously published data establishing quality of life as an independent predictor of survival across cancer sites, our results underscore the importance of quality of life surveillance in phase III clinical trials and support the inclusion of quality of life as an important component of composite clinical trial endpoints currently under development,” Dr. Phippen commented.
“Considering the independent prognostic value of the baseline FACT-O TOI score and the trend in the FACT-O TOI, methods to improve compliance with this evaluation metric are needed,” he maintained.
Patient-reported quality of life has been shown to be independently prognostic in at least five other cancers, according to Dr. Phippen. In advanced ovarian cancer, baseline FACT-O score (J. Clin. Oncol. 2005;23:5605-12) and the physical well-being scale of this score (Gynecol. Oncol. 2012;124:379-82) have previously been linked to overall survival.
In the new study, multivariate analysis that included potential confounders (age, performance status, stage, suboptimal debulking, and history of stroke or MI) showed that each 1-point decrease in baseline FACT-O TOI score was associated with significantly worse progression-free survival (hazard ratio, 1.005) and overall survival (HR, 1.0008), reported Dr. Phippen, who disclosed that he had no relevant conflicts of interest.
Additionally, within the group with lowest-quartile FACT-O TOI scores (indicating poorest quality of life), relative to peers who had a worsening of scores during treatment, women who had an improvement had significantly better progression-free survival (12.7 vs. 8.6 months) and overall survival (40.8 vs. 16 months).
Similarly, within the group having scores in higher quartiles, women who had an improvement in score during treatment again had significantly better progression-free survival (16.7 vs. 11.1 months) and overall survival (54.4 vs. 33.6 months).
CHICAGO– Quality of life at baseline and during treatment is an important prognostic factor in women with ovarian cancer, confirms an analysis reported at the annual meeting of the Society of Gynecologic Oncology.
Patients’ baseline quality of life score was independently associated with both progression-free and overall survival among 1,152 women participating in the Gynecologic Oncology Group (GOG) 218 trial, a randomized phase III trial comparing chemotherapy with versus without bevacizumab (Avastin), reported Dr. Neil T. Phippen of Walter Reed National Military Medical Center, Bethesda, Md.
Quality of life was assessed at six time points with FACT-O TOI (the Functional Assessment of Cancer Therapy–Ovarian Trial Outcome Index), on which possible scores range from 0-104 and higher scores indicate better quality of life. Women were included in analyses if they had completed the questionnaire at two or more time points.
Patients whose FACT-O TOI scores improved during treatment had a 4- to 5-month longer progression-free survival and a 20- to 25-month longer overall survival than counterparts whose scores worsened.
“Coupled with previously published data establishing quality of life as an independent predictor of survival across cancer sites, our results underscore the importance of quality of life surveillance in phase III clinical trials and support the inclusion of quality of life as an important component of composite clinical trial endpoints currently under development,” Dr. Phippen commented.
“Considering the independent prognostic value of the baseline FACT-O TOI score and the trend in the FACT-O TOI, methods to improve compliance with this evaluation metric are needed,” he maintained.
Patient-reported quality of life has been shown to be independently prognostic in at least five other cancers, according to Dr. Phippen. In advanced ovarian cancer, baseline FACT-O score (J. Clin. Oncol. 2005;23:5605-12) and the physical well-being scale of this score (Gynecol. Oncol. 2012;124:379-82) have previously been linked to overall survival.
In the new study, multivariate analysis that included potential confounders (age, performance status, stage, suboptimal debulking, and history of stroke or MI) showed that each 1-point decrease in baseline FACT-O TOI score was associated with significantly worse progression-free survival (hazard ratio, 1.005) and overall survival (HR, 1.0008), reported Dr. Phippen, who disclosed that he had no relevant conflicts of interest.
Additionally, within the group with lowest-quartile FACT-O TOI scores (indicating poorest quality of life), relative to peers who had a worsening of scores during treatment, women who had an improvement had significantly better progression-free survival (12.7 vs. 8.6 months) and overall survival (40.8 vs. 16 months).
Similarly, within the group having scores in higher quartiles, women who had an improvement in score during treatment again had significantly better progression-free survival (16.7 vs. 11.1 months) and overall survival (54.4 vs. 33.6 months).
CHICAGO– Quality of life at baseline and during treatment is an important prognostic factor in women with ovarian cancer, confirms an analysis reported at the annual meeting of the Society of Gynecologic Oncology.
Patients’ baseline quality of life score was independently associated with both progression-free and overall survival among 1,152 women participating in the Gynecologic Oncology Group (GOG) 218 trial, a randomized phase III trial comparing chemotherapy with versus without bevacizumab (Avastin), reported Dr. Neil T. Phippen of Walter Reed National Military Medical Center, Bethesda, Md.
Quality of life was assessed at six time points with FACT-O TOI (the Functional Assessment of Cancer Therapy–Ovarian Trial Outcome Index), on which possible scores range from 0-104 and higher scores indicate better quality of life. Women were included in analyses if they had completed the questionnaire at two or more time points.
Patients whose FACT-O TOI scores improved during treatment had a 4- to 5-month longer progression-free survival and a 20- to 25-month longer overall survival than counterparts whose scores worsened.
“Coupled with previously published data establishing quality of life as an independent predictor of survival across cancer sites, our results underscore the importance of quality of life surveillance in phase III clinical trials and support the inclusion of quality of life as an important component of composite clinical trial endpoints currently under development,” Dr. Phippen commented.
“Considering the independent prognostic value of the baseline FACT-O TOI score and the trend in the FACT-O TOI, methods to improve compliance with this evaluation metric are needed,” he maintained.
Patient-reported quality of life has been shown to be independently prognostic in at least five other cancers, according to Dr. Phippen. In advanced ovarian cancer, baseline FACT-O score (J. Clin. Oncol. 2005;23:5605-12) and the physical well-being scale of this score (Gynecol. Oncol. 2012;124:379-82) have previously been linked to overall survival.
In the new study, multivariate analysis that included potential confounders (age, performance status, stage, suboptimal debulking, and history of stroke or MI) showed that each 1-point decrease in baseline FACT-O TOI score was associated with significantly worse progression-free survival (hazard ratio, 1.005) and overall survival (HR, 1.0008), reported Dr. Phippen, who disclosed that he had no relevant conflicts of interest.
Additionally, within the group with lowest-quartile FACT-O TOI scores (indicating poorest quality of life), relative to peers who had a worsening of scores during treatment, women who had an improvement had significantly better progression-free survival (12.7 vs. 8.6 months) and overall survival (40.8 vs. 16 months).
Similarly, within the group having scores in higher quartiles, women who had an improvement in score during treatment again had significantly better progression-free survival (16.7 vs. 11.1 months) and overall survival (54.4 vs. 33.6 months).
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: Baseline QOL and changes in QOL during treatment are prognostic in women with ovarian cancer.
Major finding: Patients whose FACT-O TOI scores improved vs. worsened during treatment had a 4- to 5-month longer progression-free survival and a 20- to 25-month longer overall survival.
Data source: An analysis of data from 1,152 women with ovarian cancer in a randomized phase III trial.
Disclosures: Dr. Phippen disclosed that he had no relevant conflicts of interest.
Biomarker is linked to rucaparib benefit in ovarian cancer
CHICAGO – Women whose ovarian cancers harbor a BRCA mutation or have a similar genomic signature are most likely to benefit from the investigational agent rucaparib, suggest interim results of a phase II trial reported at the annual meeting of the Society of Gynecologic Oncology.
Investigators assessed activity of this novel oral PARP (poly-ADP-ribose) inhibitor in ARIEL2, A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. The study was sponsored by Clovis Oncology, manufacturer of rucaparib.
They also tested a biomarker of homologous recombination deficiency (HRD), which confers susceptibility to PARP inhibitors and is commonly seen in BRCA-mutated tumors, said Dr. Elizabeth Swisher, medical director of the breast and ovarian cancer prevention program at the Seattle Cancer Care Alliance and a professor at the University of Washington, Seattle.
Tumors were genomically profiled with next-generation sequencing, which picks up the loss of heterozygosity caused by HRD, whether specifically due to a BRCA mutation or to other molecular aberrations that give tumors a similar genomic signature.
Results in the first 121 evaluable patients showed that 25% had tumors with a BRCA mutation (a percentage capped in the study) and 42% had tumors that lacked such mutation but nonetheless had a BRCA-like signature, while 33% had tumors negative for the biomarker, Dr. Swisher reported.
The response rate to rucaparib according to RECIST (Response Evaluation Criteria In Solid Tumors) was 43% among 61 evaluable patients overall. But it varied significantly by HRD biomarker status: It was 65% in those with BRCA-mutated tumors and 40% in those with a BRCA-like signature, but only 8% in those with tumors negative for the biomarker (P less than .001).
The most common treatment-related adverse events were nausea, fatigue, and transient elevation of liver function tests. None of the patients stopped treatment because of toxicity.
“Rucaparib is active and well tolerated in high-grade ovarian cancer,” summarized Dr. Swisher.
“Comprehensive genomic analysis of the tumor based on a next-generation sequencing platform can prospectively identify ovarian cancer patients who respond to rucaparib, and it identifies both relevant BRCA mutations and a BRCA-like signature in one test,” she said. “The BRCA-like signature could have utility in other cancer types beyond ovarian cancer, potentially.”
She noted that ARIEL2 has recently been expanded to be a registration study for the treatment of patients with ovarian cancer who have had failure of three prior therapies, regardless of BRCA mutational status, and remains open for enrollment.
Investigators with the ARIEL program are refining the HRD biomarker, according to Dr. Swisher. “We will look at different cutoffs to see if we can get an even better cutoff for defining the BRCA-like cases. That biomarker will be locked down and tested prospectively in ARIEL3, which is the pivotal phase III, randomized, placebo-controlled study – recurrent, maintenance, platinum sensitive – that hopefully will be a registration study,” she elaborated.
Dr. Swisher disclosed that she had no relevant conflicts of interest. The trial was sponsored by Clovis Oncology.
CHICAGO – Women whose ovarian cancers harbor a BRCA mutation or have a similar genomic signature are most likely to benefit from the investigational agent rucaparib, suggest interim results of a phase II trial reported at the annual meeting of the Society of Gynecologic Oncology.
Investigators assessed activity of this novel oral PARP (poly-ADP-ribose) inhibitor in ARIEL2, A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. The study was sponsored by Clovis Oncology, manufacturer of rucaparib.
They also tested a biomarker of homologous recombination deficiency (HRD), which confers susceptibility to PARP inhibitors and is commonly seen in BRCA-mutated tumors, said Dr. Elizabeth Swisher, medical director of the breast and ovarian cancer prevention program at the Seattle Cancer Care Alliance and a professor at the University of Washington, Seattle.
Tumors were genomically profiled with next-generation sequencing, which picks up the loss of heterozygosity caused by HRD, whether specifically due to a BRCA mutation or to other molecular aberrations that give tumors a similar genomic signature.
Results in the first 121 evaluable patients showed that 25% had tumors with a BRCA mutation (a percentage capped in the study) and 42% had tumors that lacked such mutation but nonetheless had a BRCA-like signature, while 33% had tumors negative for the biomarker, Dr. Swisher reported.
The response rate to rucaparib according to RECIST (Response Evaluation Criteria In Solid Tumors) was 43% among 61 evaluable patients overall. But it varied significantly by HRD biomarker status: It was 65% in those with BRCA-mutated tumors and 40% in those with a BRCA-like signature, but only 8% in those with tumors negative for the biomarker (P less than .001).
The most common treatment-related adverse events were nausea, fatigue, and transient elevation of liver function tests. None of the patients stopped treatment because of toxicity.
“Rucaparib is active and well tolerated in high-grade ovarian cancer,” summarized Dr. Swisher.
“Comprehensive genomic analysis of the tumor based on a next-generation sequencing platform can prospectively identify ovarian cancer patients who respond to rucaparib, and it identifies both relevant BRCA mutations and a BRCA-like signature in one test,” she said. “The BRCA-like signature could have utility in other cancer types beyond ovarian cancer, potentially.”
She noted that ARIEL2 has recently been expanded to be a registration study for the treatment of patients with ovarian cancer who have had failure of three prior therapies, regardless of BRCA mutational status, and remains open for enrollment.
Investigators with the ARIEL program are refining the HRD biomarker, according to Dr. Swisher. “We will look at different cutoffs to see if we can get an even better cutoff for defining the BRCA-like cases. That biomarker will be locked down and tested prospectively in ARIEL3, which is the pivotal phase III, randomized, placebo-controlled study – recurrent, maintenance, platinum sensitive – that hopefully will be a registration study,” she elaborated.
Dr. Swisher disclosed that she had no relevant conflicts of interest. The trial was sponsored by Clovis Oncology.
CHICAGO – Women whose ovarian cancers harbor a BRCA mutation or have a similar genomic signature are most likely to benefit from the investigational agent rucaparib, suggest interim results of a phase II trial reported at the annual meeting of the Society of Gynecologic Oncology.
Investigators assessed activity of this novel oral PARP (poly-ADP-ribose) inhibitor in ARIEL2, A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. The study was sponsored by Clovis Oncology, manufacturer of rucaparib.
They also tested a biomarker of homologous recombination deficiency (HRD), which confers susceptibility to PARP inhibitors and is commonly seen in BRCA-mutated tumors, said Dr. Elizabeth Swisher, medical director of the breast and ovarian cancer prevention program at the Seattle Cancer Care Alliance and a professor at the University of Washington, Seattle.
Tumors were genomically profiled with next-generation sequencing, which picks up the loss of heterozygosity caused by HRD, whether specifically due to a BRCA mutation or to other molecular aberrations that give tumors a similar genomic signature.
Results in the first 121 evaluable patients showed that 25% had tumors with a BRCA mutation (a percentage capped in the study) and 42% had tumors that lacked such mutation but nonetheless had a BRCA-like signature, while 33% had tumors negative for the biomarker, Dr. Swisher reported.
The response rate to rucaparib according to RECIST (Response Evaluation Criteria In Solid Tumors) was 43% among 61 evaluable patients overall. But it varied significantly by HRD biomarker status: It was 65% in those with BRCA-mutated tumors and 40% in those with a BRCA-like signature, but only 8% in those with tumors negative for the biomarker (P less than .001).
The most common treatment-related adverse events were nausea, fatigue, and transient elevation of liver function tests. None of the patients stopped treatment because of toxicity.
“Rucaparib is active and well tolerated in high-grade ovarian cancer,” summarized Dr. Swisher.
“Comprehensive genomic analysis of the tumor based on a next-generation sequencing platform can prospectively identify ovarian cancer patients who respond to rucaparib, and it identifies both relevant BRCA mutations and a BRCA-like signature in one test,” she said. “The BRCA-like signature could have utility in other cancer types beyond ovarian cancer, potentially.”
She noted that ARIEL2 has recently been expanded to be a registration study for the treatment of patients with ovarian cancer who have had failure of three prior therapies, regardless of BRCA mutational status, and remains open for enrollment.
Investigators with the ARIEL program are refining the HRD biomarker, according to Dr. Swisher. “We will look at different cutoffs to see if we can get an even better cutoff for defining the BRCA-like cases. That biomarker will be locked down and tested prospectively in ARIEL3, which is the pivotal phase III, randomized, placebo-controlled study – recurrent, maintenance, platinum sensitive – that hopefully will be a registration study,” she elaborated.
Dr. Swisher disclosed that she had no relevant conflicts of interest. The trial was sponsored by Clovis Oncology.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: A biomarker identified women with ovarian cancer most likely to have a response to rucaparib.
Major finding: The response rate was 65% in women whose tumors had a BRCA mutation and 40% in women whose tumors had a BRCA-like genomic signature.
Data source: An interim analysis of a phase II trial with data from 121 women with high-grade platinum-sensitive ovarian cancer.
Disclosures: Dr. Swisher disclosed that she had no relevant conflicts of interest. The trial was sponsored by Clovis Oncology.
Model accurately spots low-risk endometrial cancer
CHICAGO – A preoperative risk model accurately identifies women with endometrial cancer who are unlikely to have lymph node metastases, finds a prospective cohort study reported at the annual Meeting of the Society of Gynecologic Oncology.
The model – which uses favorable MRI features, endometrioid histology on biopsy, and a cancer antigen 125 (CA125) level of 35 U/mL or lower to define a low-risk group – had a negative predictive value of 97% when tested in 529 Asian women.
“Using [our model], we can reliably identify patients with a low risk for lymph node metastasis before surgery,” said Dr. Sokbom Kang, director of the division of gynecologic oncology at the National Cancer Center, Goyang, Korea.
“In the clinic, our preoperative risk assessment may be useful in patient counseling. By sharing this risk information with our patients, we may improve their decision-making process about their surgery,” he added. “Not only does it help patient counseling and surgical planning, but it also may be useful in patient selection for future surgical trials.”
Some guidelines have stopped recommending routine lymphadenectomy in patients with endometrial cancer, according to Dr. Kang. “However, some experts still endorse this procedure, even in low-risk patients. Their argument is, low-risk patients cannot be accurately identified because preoperative tests are inaccurate.”
The risk model was developed by the Korean Gynecologic Oncology group (J. Clin. Oncol. 2012;30:1329-34) and has since been validated in smaller single-nationality cohorts.
In the new study, known as PALME (Preoperative Risk Assessment for Lymph Node Metastasis in Endometrial Cancer), it was tested among consecutive women from 25 hospitals in Korea, Japan, and China who had a histologic diagnosis of endometrial cancer. Those with squamous cell carcinoma or sarcoma histologies were excluded.
The women underwent MRI and CA125 testing in the 4 weeks before surgery. They had surgical staging with pelvic lymphadenectomy, and para-aortic lymphadenectomy was recommended. The median number of nodes removed was 23.
Results showed that the model classified 51% of the patients as having a low risk of lymph node metastases, reported Dr. Kang, who disclosed that he had no relevant conflicts of interest.
On the basis of surgical findings, the model had a negative predictive value of 97%, corresponding to a false-negative predictive rate of just 3%, which was in line with earlier results seen in the smaller validation studies.
In a receiver operating characteristic curve analysis, the model had a summarized sensitivity of 91% and a summarized specificity of 54%.
The performance was similar when tumor grade was substituted for CA125 level, except that specificity decreased significantly. “The lower specificity means fewer patients will benefit from our selective lymphadenectomy strategy, so it impairs the cost-effectiveness of our strategy,” Dr. Kang said.
The model performed similarly as well as a model using features of the primary tumor drawn from the final pathology report. “This proves our preoperative risk assessment has similar accuracy to the postoperative risk assessment for identifying a low risk of lymph node metastasis,” he concluded.
CHICAGO – A preoperative risk model accurately identifies women with endometrial cancer who are unlikely to have lymph node metastases, finds a prospective cohort study reported at the annual Meeting of the Society of Gynecologic Oncology.
The model – which uses favorable MRI features, endometrioid histology on biopsy, and a cancer antigen 125 (CA125) level of 35 U/mL or lower to define a low-risk group – had a negative predictive value of 97% when tested in 529 Asian women.
“Using [our model], we can reliably identify patients with a low risk for lymph node metastasis before surgery,” said Dr. Sokbom Kang, director of the division of gynecologic oncology at the National Cancer Center, Goyang, Korea.
“In the clinic, our preoperative risk assessment may be useful in patient counseling. By sharing this risk information with our patients, we may improve their decision-making process about their surgery,” he added. “Not only does it help patient counseling and surgical planning, but it also may be useful in patient selection for future surgical trials.”
Some guidelines have stopped recommending routine lymphadenectomy in patients with endometrial cancer, according to Dr. Kang. “However, some experts still endorse this procedure, even in low-risk patients. Their argument is, low-risk patients cannot be accurately identified because preoperative tests are inaccurate.”
The risk model was developed by the Korean Gynecologic Oncology group (J. Clin. Oncol. 2012;30:1329-34) and has since been validated in smaller single-nationality cohorts.
In the new study, known as PALME (Preoperative Risk Assessment for Lymph Node Metastasis in Endometrial Cancer), it was tested among consecutive women from 25 hospitals in Korea, Japan, and China who had a histologic diagnosis of endometrial cancer. Those with squamous cell carcinoma or sarcoma histologies were excluded.
The women underwent MRI and CA125 testing in the 4 weeks before surgery. They had surgical staging with pelvic lymphadenectomy, and para-aortic lymphadenectomy was recommended. The median number of nodes removed was 23.
Results showed that the model classified 51% of the patients as having a low risk of lymph node metastases, reported Dr. Kang, who disclosed that he had no relevant conflicts of interest.
On the basis of surgical findings, the model had a negative predictive value of 97%, corresponding to a false-negative predictive rate of just 3%, which was in line with earlier results seen in the smaller validation studies.
In a receiver operating characteristic curve analysis, the model had a summarized sensitivity of 91% and a summarized specificity of 54%.
The performance was similar when tumor grade was substituted for CA125 level, except that specificity decreased significantly. “The lower specificity means fewer patients will benefit from our selective lymphadenectomy strategy, so it impairs the cost-effectiveness of our strategy,” Dr. Kang said.
The model performed similarly as well as a model using features of the primary tumor drawn from the final pathology report. “This proves our preoperative risk assessment has similar accuracy to the postoperative risk assessment for identifying a low risk of lymph node metastasis,” he concluded.
CHICAGO – A preoperative risk model accurately identifies women with endometrial cancer who are unlikely to have lymph node metastases, finds a prospective cohort study reported at the annual Meeting of the Society of Gynecologic Oncology.
The model – which uses favorable MRI features, endometrioid histology on biopsy, and a cancer antigen 125 (CA125) level of 35 U/mL or lower to define a low-risk group – had a negative predictive value of 97% when tested in 529 Asian women.
“Using [our model], we can reliably identify patients with a low risk for lymph node metastasis before surgery,” said Dr. Sokbom Kang, director of the division of gynecologic oncology at the National Cancer Center, Goyang, Korea.
“In the clinic, our preoperative risk assessment may be useful in patient counseling. By sharing this risk information with our patients, we may improve their decision-making process about their surgery,” he added. “Not only does it help patient counseling and surgical planning, but it also may be useful in patient selection for future surgical trials.”
Some guidelines have stopped recommending routine lymphadenectomy in patients with endometrial cancer, according to Dr. Kang. “However, some experts still endorse this procedure, even in low-risk patients. Their argument is, low-risk patients cannot be accurately identified because preoperative tests are inaccurate.”
The risk model was developed by the Korean Gynecologic Oncology group (J. Clin. Oncol. 2012;30:1329-34) and has since been validated in smaller single-nationality cohorts.
In the new study, known as PALME (Preoperative Risk Assessment for Lymph Node Metastasis in Endometrial Cancer), it was tested among consecutive women from 25 hospitals in Korea, Japan, and China who had a histologic diagnosis of endometrial cancer. Those with squamous cell carcinoma or sarcoma histologies were excluded.
The women underwent MRI and CA125 testing in the 4 weeks before surgery. They had surgical staging with pelvic lymphadenectomy, and para-aortic lymphadenectomy was recommended. The median number of nodes removed was 23.
Results showed that the model classified 51% of the patients as having a low risk of lymph node metastases, reported Dr. Kang, who disclosed that he had no relevant conflicts of interest.
On the basis of surgical findings, the model had a negative predictive value of 97%, corresponding to a false-negative predictive rate of just 3%, which was in line with earlier results seen in the smaller validation studies.
In a receiver operating characteristic curve analysis, the model had a summarized sensitivity of 91% and a summarized specificity of 54%.
The performance was similar when tumor grade was substituted for CA125 level, except that specificity decreased significantly. “The lower specificity means fewer patients will benefit from our selective lymphadenectomy strategy, so it impairs the cost-effectiveness of our strategy,” Dr. Kang said.
The model performed similarly as well as a model using features of the primary tumor drawn from the final pathology report. “This proves our preoperative risk assessment has similar accuracy to the postoperative risk assessment for identifying a low risk of lymph node metastasis,” he concluded.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: A preoperative risk model may help identify women with endometrial cancer who can skip lymphadenectomy.
Major finding: The model had a negative predictive value of 97%.
Data source: A prospective cohort study of 529 Asian women with endometrial cancer.
Disclosures: Dr. Kang disclosed that he had no relevant conflicts of interest.
SLN mapping found accurate in endometrial cancer
CHICAGO – Sentinel lymph node mapping alone may suffice for initial staging in women with clinical high-risk endometrial cancer, according to a prospective cohort study reported at the annual meeting of the Society of Gynecologic Oncology.
“While the majority of women with endometrial cancer do not have nodal involvement, positive nodes are an important prognostic factor and often guide postoperative adjuvant therapy. The use of SLN [sentinel lymph node] mapping could potentially maximize the identification of positive nodes while minimizing the risk of full lymphadenectomy,” noted Dr. Pamela T. Soliman, Center Medical Director of the Gynecologic Medical Center at The University of Texas MD Anderson Cancer Center, Houston.
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| Susan London/Frontline Medical News |
Dr. Pamela Soliman |
She and her colleagues studied 60 women who had clinical stage II disease with high-risk features on preoperative biopsy. All women underwent preoperative PET-CT, then SLN mapping, and finally a full surgical staging with pelvic and para-aortic lymphadenectomy to the renal vessels.
Results showed that 92% of women had at least one SLN detected and 61% had SLNs detected bilaterally. “These findings are consistent with others reported in the literature suggesting that this technique is reproducible,” Dr. Soliman maintained.
Importantly, she said, all of the patients ultimately found to have stage IIIc disease had at least one positive SLN identified, translating to a sensitivity of SLN mapping of 100% and a false-negative rate of zero.
“While we do not expect that the true false-negative rate is zero in this patient population, our results are very promising, and we are hopeful that with our study and other studies presented here, we can potentially change the way we manage patients with high-risk endometrial cancer,” she said.
“If we continue to successfully identify the women with positive lymph nodes using the mapping technique, potentially an SLN biopsy alone could be considered for women with high-risk endometrial cancer. It’s unclear, however, how this change in practice will affect our postoperative management as well as our long-term survival,” Dr. Soliman added.
The SLN mapping in the study was done with a cervical injection of dye, both superficial and deep, at the 3 and 9 o’clock positions, with the surgical approach (laparotomy, laparoscopy, robot-assisted, or a combination) and type of dye used for mapping left up to the surgeon. Indocyanine green was used in about two-thirds of cases.
The high SLN detection rate was consistent across different surgical approaches and types of dye used, reported Dr. Soliman, who disclosed that she had no relevant conflicts of interest.
A total of 146 SLNs were identified in 56 women. Seventeen of these SLNs – all external iliac or obturator nodes – in 10 patients were positive; in half of these patients, the SLNs were the only histologically positive nodes found.
One woman had a negative SLN on the right, although the non-SLNs on that side were positive. “She was not considered a false-negative because her SLN biopsy on the other side was positive,” Dr. Soliman explained.
CHICAGO – Sentinel lymph node mapping alone may suffice for initial staging in women with clinical high-risk endometrial cancer, according to a prospective cohort study reported at the annual meeting of the Society of Gynecologic Oncology.
“While the majority of women with endometrial cancer do not have nodal involvement, positive nodes are an important prognostic factor and often guide postoperative adjuvant therapy. The use of SLN [sentinel lymph node] mapping could potentially maximize the identification of positive nodes while minimizing the risk of full lymphadenectomy,” noted Dr. Pamela T. Soliman, Center Medical Director of the Gynecologic Medical Center at The University of Texas MD Anderson Cancer Center, Houston.
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| Susan London/Frontline Medical News |
Dr. Pamela Soliman |
She and her colleagues studied 60 women who had clinical stage II disease with high-risk features on preoperative biopsy. All women underwent preoperative PET-CT, then SLN mapping, and finally a full surgical staging with pelvic and para-aortic lymphadenectomy to the renal vessels.
Results showed that 92% of women had at least one SLN detected and 61% had SLNs detected bilaterally. “These findings are consistent with others reported in the literature suggesting that this technique is reproducible,” Dr. Soliman maintained.
Importantly, she said, all of the patients ultimately found to have stage IIIc disease had at least one positive SLN identified, translating to a sensitivity of SLN mapping of 100% and a false-negative rate of zero.
“While we do not expect that the true false-negative rate is zero in this patient population, our results are very promising, and we are hopeful that with our study and other studies presented here, we can potentially change the way we manage patients with high-risk endometrial cancer,” she said.
“If we continue to successfully identify the women with positive lymph nodes using the mapping technique, potentially an SLN biopsy alone could be considered for women with high-risk endometrial cancer. It’s unclear, however, how this change in practice will affect our postoperative management as well as our long-term survival,” Dr. Soliman added.
The SLN mapping in the study was done with a cervical injection of dye, both superficial and deep, at the 3 and 9 o’clock positions, with the surgical approach (laparotomy, laparoscopy, robot-assisted, or a combination) and type of dye used for mapping left up to the surgeon. Indocyanine green was used in about two-thirds of cases.
The high SLN detection rate was consistent across different surgical approaches and types of dye used, reported Dr. Soliman, who disclosed that she had no relevant conflicts of interest.
A total of 146 SLNs were identified in 56 women. Seventeen of these SLNs – all external iliac or obturator nodes – in 10 patients were positive; in half of these patients, the SLNs were the only histologically positive nodes found.
One woman had a negative SLN on the right, although the non-SLNs on that side were positive. “She was not considered a false-negative because her SLN biopsy on the other side was positive,” Dr. Soliman explained.
CHICAGO – Sentinel lymph node mapping alone may suffice for initial staging in women with clinical high-risk endometrial cancer, according to a prospective cohort study reported at the annual meeting of the Society of Gynecologic Oncology.
“While the majority of women with endometrial cancer do not have nodal involvement, positive nodes are an important prognostic factor and often guide postoperative adjuvant therapy. The use of SLN [sentinel lymph node] mapping could potentially maximize the identification of positive nodes while minimizing the risk of full lymphadenectomy,” noted Dr. Pamela T. Soliman, Center Medical Director of the Gynecologic Medical Center at The University of Texas MD Anderson Cancer Center, Houston.
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| Susan London/Frontline Medical News |
Dr. Pamela Soliman |
She and her colleagues studied 60 women who had clinical stage II disease with high-risk features on preoperative biopsy. All women underwent preoperative PET-CT, then SLN mapping, and finally a full surgical staging with pelvic and para-aortic lymphadenectomy to the renal vessels.
Results showed that 92% of women had at least one SLN detected and 61% had SLNs detected bilaterally. “These findings are consistent with others reported in the literature suggesting that this technique is reproducible,” Dr. Soliman maintained.
Importantly, she said, all of the patients ultimately found to have stage IIIc disease had at least one positive SLN identified, translating to a sensitivity of SLN mapping of 100% and a false-negative rate of zero.
“While we do not expect that the true false-negative rate is zero in this patient population, our results are very promising, and we are hopeful that with our study and other studies presented here, we can potentially change the way we manage patients with high-risk endometrial cancer,” she said.
“If we continue to successfully identify the women with positive lymph nodes using the mapping technique, potentially an SLN biopsy alone could be considered for women with high-risk endometrial cancer. It’s unclear, however, how this change in practice will affect our postoperative management as well as our long-term survival,” Dr. Soliman added.
The SLN mapping in the study was done with a cervical injection of dye, both superficial and deep, at the 3 and 9 o’clock positions, with the surgical approach (laparotomy, laparoscopy, robot-assisted, or a combination) and type of dye used for mapping left up to the surgeon. Indocyanine green was used in about two-thirds of cases.
The high SLN detection rate was consistent across different surgical approaches and types of dye used, reported Dr. Soliman, who disclosed that she had no relevant conflicts of interest.
A total of 146 SLNs were identified in 56 women. Seventeen of these SLNs – all external iliac or obturator nodes – in 10 patients were positive; in half of these patients, the SLNs were the only histologically positive nodes found.
One woman had a negative SLN on the right, although the non-SLNs on that side were positive. “She was not considered a false-negative because her SLN biopsy on the other side was positive,” Dr. Soliman explained.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: SLN mapping had a false-negative rate of zero.
Major finding: The SLN mapping procedure identified all cases of pathologic stage IIIc disease.
Data source: A prospective cohort study of 60 women with clinical stage II high-risk endometrial cancer.
Disclosures: Dr. Soliman disclosed that she had no conflicts of interest.
