Pembrolizumab Plus Weekly Paclitaxel in Keynote-B96 Recurrent Ovarian Cancer

Key Takeaways

• Progression-free survival improved at the first interim analysis in both the PD-L1 CPS 1 or higher population and the overall population.
• Overall survival improved at the second interim analysis in the PD-L1 CPS 1 or higher population and at the final analysis in the overall population.
• Grade 3 or worse treatment-related adverse events were more frequent with pembrolizumab plus paclitaxel, and treatment-related deaths occurred in both groups.

In women with platinum-resistant recurrent ovarian cancer after prior systemic therapy, pembrolizumab plus weekly paclitaxel, with or without bevacizumab, was associated with longer median progression-free survival than placebo plus weekly paclitaxel, with or without bevacizumab, 8.3 versus 6.4 months, in the overall population. Investigators also reported a hazard ratio of 0.70, and overall survival improved later in the analysis sequence. The randomized phase 3 trial used the same weekly paclitaxel backbone in both groups, with bevacizumab permitted at investigator discretion during study treatment.

The ENGOT-ov65/KEYNOTE-B96 abstract describes a multicentre randomized double-blind phase 3 study conducted at 187 gynecologic oncology centres in 25 countries. Eligible women were 18 years or older with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Participants had received one to two previous systemic therapies, including at least one platinum regimen, and had progression within 6 months of the last platinum regimen. Researchers randomly assigned 643 participants, with 322 to pembrolizumab 400 mg every 6 weeks for up to 18 cycles plus paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle. The 321 control participants received placebo on the same schedule plus paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle, and bevacizumab 10 mg/kg every 2 weeks was permitted per investigator in both groups.

Randomization was stratified by planned bevacizumab use, region, and PD-L1 combined positive score, and investigator-assessed progression-free survival per RECIST 1.1 was the primary endpoint. Overall survival was the key secondary endpoint. At the first interim analysis, median progression-free survival in PD-L1 CPS 1 or higher disease was 8.3 versus 7.2 months. The hazard ratio was 0.72, with a 95% confidence interval of 0.58 to 0.89, p=0.0014, and progression-free survival also improved in the overall population. At the second interim analysis, overall survival in PD-L1 CPS 1 or higher disease was 18.2 versus 14.0 months, HR 0.76, 95% CI 0.61-0.94, p=0.0053. Final overall-population overall survival was 17.7 versus 14.0 months, HR 0.82, 95% CI 0.69-0.97, p=0.011, with reported benefit across progression-free and overall survival endpoints.

Grade 3 or worse treatment-related adverse events occurred in 217 of 320 participants, or 68%, in the pembrolizumab arm and 176 of 318, or 55%, in the placebo arm. The most common treatment-related adverse events of any grade were anaemia, peripheral neuropathy, alopecia, fatigue, and nausea. Treatment-related adverse events resulted in death in four participants, or 1%, in the pembrolizumab arm and five participants, or 2%, in the placebo arm. Listed causes included colitis, interstitial lung disease, acute myeloid leukaemia, cardiac failure, intestinal perforation, and large-intestine perforation. Treatment-related deaths occurred in both study groups.

The authors interpreted pembrolizumab plus weekly paclitaxel, with or without bevacizumab, as a new treatment option for platinum-resistant recurrent ovarian cancer.