Pembrolizumab Plus Chemo Boosts PFS, OS in Platinum-Resistant Recurrent Ovarian Cancer: Nicoletta Colombo, MD, PhD

Nicoletta Colombo, MD, PhD, associate professor of obstetrics and gynecology at the University of Milan-Bicocca, director of the Ovarian Cancer Centre, and chair of the Program of Gynecology at the European Institute of Oncology, discusses key outcomes in the KEYNOTE-B96 trial of pembrolizumab (Keytruda; Merck) plus chemotherapy in platinum-resistant recurrent ovarian cancer. New data presented at the European Society for Medical Oncology Annual Congress 2025 showed overall survival (OS) improvement, as well as one of the longest observed progression-free survival (PFS) outcomes in this patient population, Colombo said.

This transcript has been lightly edited; captions are auto-generated.

Transcript

Could you summarize the results of the study—particularly how progression-free survival and overall survival compared across the treatment arms?

In our study, we first of all included 643 patients. We randomized 643 patients, and 322 were allocated to the pembrolizumab arm and 321 to the placebo arm. And I have to say something about the statistical plan of this study, because we had 2 primary hypotheses to test, which were the PFS in the CPS [Combined Positive Score] 1 and higher population, and in the intention-to-treat population. We allocated alpha to these 2 hypotheses with the possibility to pass the alpha to subsequent hypotheses on OS in case of successful demonstration of the PFS results.

At interim analysis 1, we looked at the progression-free survival in the CPS 1 and higher population, and we were able to demonstrate a statistically significant and clinically meaningful improvement in survival in this population with a CPS score of 1 and higher, with a hazard ratio of 0.72 and a P value of .0014, which crossed the prespecified nominal boundary for significance. Then we looked at the intention-to-treat population, and also in the intention-to-treat population, there was a statistically significant improvement with the addition of pembrolizumab to weekly paclitaxel compared to placebo, with a hazard ratio of .70 for progression-free survival and a P value less than .0001.

But I think even more important is the overall survival. Overall survival was a key secondary end point, and since the 2 primary hypotheses were successful, then we tested OS. At this interim analysis 2 in the CPS 1 and higher population, there was a significant improvement in overall survival for the CPS 1 and higher population, with a hazard ratio of 0.76, and the median overall survival was 18 months for the pembrolizumab arm and 14 months for the placebo. I want to stress this point, because 18 months is one of the longest OS observed in this population, and also the 4-month difference that we observed is relative to a very highly performing control arm, which is kind of unique, I think, in this study. Up to a few minutes ago, a few hours ago, there was a press release announcing that the overall survival in the intention-to-treat population is also positive, so the addition of pembrolizumab to paclitaxel in the intention-to-treat showed an improvement in overall survival. This, of course, is a very important achievement for our patients.

How did the addition of pembrolizumab affect the tolerability profile compared with chemotherapy alone or chemotherapy plus bevacizumab?

If we look at the adverse events of all-cause and treatment-related, there was a slight increase—a numerical increase—in the incident side effects of grade 3 and serious adverse events. However, the treatment exposure was longer for the pembrolizumab arm: 33 weeks compared to 28 weeks in the placebo arm. Of course, if you look at the immune-mediated adverse events, these were more frequent in the pembrolizumab arm, but most of them were really low grade and manageable. If you look at the treatment-related adverse events, actually, we didn't see any difference across the 2 arms. The most frequent treatment-related adverse events were anemia and peripheral neuronal alopecia, and these were mainly due to weekly paclitaxel. If we look at the immune-mediated adverse events, they were mostly hypothyroidism, infusion reaction, and adrenal insufficiency, but most of them were really very low grade and easily manageable with those adjustments and also the use of concomitant medications. We also had data on quality of life, and we showed that there was no detrimental effect on the quality of life. I think overall, the safety profile of this regimen is consistent with the known profiles of the individual therapies, and there were no new safety signals.

Reference

Colombo N, Zsiros E. Sebastianelli A, et al. Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer: Results from the randomized double-blind phase III ENGOT-ov65/KEYNOTE-B96 study. Presented at: 50th European Society for Medical Oncology Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA3.