Background Epithelial ovarian cancer frequently recurs and becomes resistant to platinum chemotherapy. We investigated whether adding pembrolizumab to weekly paclitaxel, with or without bevacizumab, improves progression-free survival and overall survival compared with weekly paclitaxel, with or without bevacizumab, in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens. Methods ENGOT-ov65/KEYNOTE-B96 is a randomised, double-blind, phase 3 study conducted at 187 gynaecologic oncology centres in 25 countries in the Americas, Asia, Europe, and Oceania. Adults (≥18 years) with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who received one to two previous systemic therapies including at least one platinum regimen and who progressed 6 months or less after the last platinum regimen, were eligible. Participants were randomly assigned 1:1 to intravenous pembrolizumab 400 mg every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle or intravenous placebo (saline solution) every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle; intravenous bevacizumab 10 mg/kg every 2 weeks was permitted per investigator. Randomisation was stratified by planned bevacizumab use, region, and PD-L1 combined positive score (CPS). The primary endpoint was investigator-assessed progression-free survival per RECIST version 1.1; the key secondary endpoint was overall survival. Results from two interim analyses and the final analysis are included in this Article. This study is registered with ClinicalTrials.gov , NCT05116189 , and is now completed. Findings Between Dec 13, 2021, and July 3, 2023, 643 female participants were randomly assigned; 322 to pembrolizumab plus paclitaxel and 321 to placebo plus paclitaxel. At the first interim analysis, pembrolizumab plus paclitaxel significantly improved progression-free survival versus placebo plus paclitaxel in both the PD-L1 CPS 1 or higher (median 8·3 months vs 7·2 months; hazard ratio [HR] 0·72; 95% CI 0·58–0·89; p=0·0014 α=0·012]) and overall populations (median 8·3 months vs 6·4 months; HR 0·70, 95% CI 0·58–0·84; p<0·0001, [α=0·0023]), meeting the prespecified criteria for confirmatory efficacy. At the second interim analysis, overall survival was significantly improved in the PD-L1 CPS 1 or higher population (median 18·2 months vs 14·0 months; HR 0·76, 95% CI 0·61–0·94; p=0·0053, [α=0·0083]). At the final analysis, overall survival was significantly improved in the overall population (median 17·7 months vs 14·0 months; HR 0·82, 95% CI 0·69–0·97; p=0·011 [α=0·024]). Grade 3 or worse treatment-related adverse events occurred in 217 (68%) of 320 participants in the pembrolizumab plus paclitaxel group versus 176 (55%) of 318 participants in the placebo plus paclitaxel group. The most common treatment-related adverse events (any grade) included anaemia, peripheral neuropathy, alopecia, fatigue, and nausea. Treatment-related adverse events resulted in death in four participants (1%) in the pembrolizumab plus paclitaxel group (colitis, interstitial lung disease, acute myeloid leukaemia, and intestinal perforation) and in five participants (2%) in the placebo plus paclitaxel group (cardiac failure, intestinal perforation [in two participants], and large-intestine perforation [in two participants]). Interpretation Pembrolizumab plus weekly paclitaxel, with or without bevacizumab, significantly improved progression-free survival and overall survival in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens, supporting this regimen as a new treatment option for this population. Funding Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA.
Pembrolizumab plus weekly paclitaxel in platinum-resistant recurrent ovarian cancer (ENGOT-ov65/KEYNOTE-B96): a multicentre, randomised, double-blind, phase 3 study
Ferrero, Annamaria;
2026-01-01
Abstract
Background Epithelial ovarian cancer frequently recurs and becomes resistant to platinum chemotherapy. We investigated whether adding pembrolizumab to weekly paclitaxel, with or without bevacizumab, improves progression-free survival and overall survival compared with weekly paclitaxel, with or without bevacizumab, in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens. Methods ENGOT-ov65/KEYNOTE-B96 is a randomised, double-blind, phase 3 study conducted at 187 gynaecologic oncology centres in 25 countries in the Americas, Asia, Europe, and Oceania. Adults (≥18 years) with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who received one to two previous systemic therapies including at least one platinum regimen and who progressed 6 months or less after the last platinum regimen, were eligible. Participants were randomly assigned 1:1 to intravenous pembrolizumab 400 mg every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle or intravenous placebo (saline solution) every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle; intravenous bevacizumab 10 mg/kg every 2 weeks was permitted per investigator. Randomisation was stratified by planned bevacizumab use, region, and PD-L1 combined positive score (CPS). The primary endpoint was investigator-assessed progression-free survival per RECIST version 1.1; the key secondary endpoint was overall survival. Results from two interim analyses and the final analysis are included in this Article. This study is registered with ClinicalTrials.gov , NCT05116189 , and is now completed. Findings Between Dec 13, 2021, and July 3, 2023, 643 female participants were randomly assigned; 322 to pembrolizumab plus paclitaxel and 321 to placebo plus paclitaxel. At the first interim analysis, pembrolizumab plus paclitaxel significantly improved progression-free survival versus placebo plus paclitaxel in both the PD-L1 CPS 1 or higher (median 8·3 months vs 7·2 months; hazard ratio [HR] 0·72; 95% CI 0·58–0·89; p=0·0014 α=0·012]) and overall populations (median 8·3 months vs 6·4 months; HR 0·70, 95% CI 0·58–0·84; p<0·0001, [α=0·0023]), meeting the prespecified criteria for confirmatory efficacy. At the second interim analysis, overall survival was significantly improved in the PD-L1 CPS 1 or higher population (median 18·2 months vs 14·0 months; HR 0·76, 95% CI 0·61–0·94; p=0·0053, [α=0·0083]). At the final analysis, overall survival was significantly improved in the overall population (median 17·7 months vs 14·0 months; HR 0·82, 95% CI 0·69–0·97; p=0·011 [α=0·024]). Grade 3 or worse treatment-related adverse events occurred in 217 (68%) of 320 participants in the pembrolizumab plus paclitaxel group versus 176 (55%) of 318 participants in the placebo plus paclitaxel group. The most common treatment-related adverse events (any grade) included anaemia, peripheral neuropathy, alopecia, fatigue, and nausea. Treatment-related adverse events resulted in death in four participants (1%) in the pembrolizumab plus paclitaxel group (colitis, interstitial lung disease, acute myeloid leukaemia, and intestinal perforation) and in five participants (2%) in the placebo plus paclitaxel group (cardiac failure, intestinal perforation [in two participants], and large-intestine perforation [in two participants]). Interpretation Pembrolizumab plus weekly paclitaxel, with or without bevacizumab, significantly improved progression-free survival and overall survival in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens, supporting this regimen as a new treatment option for this population. Funding Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
