Weekly Paclitaxel May Hold the Key to Pembrolizumab’s Success in Platinum-Resistance Ovarian Cancer

In an interview with Pharmacy Times, Nicoletta Colombo, MD, PhD, reflected on the design and implications of the phase 3 KEYNOTE-B96 trial, which showed a survival benefit with pembrolizumab (Keytruda; Merck) plus chemotherapy and bevacizumab (Avastin; Genentech) in patients with platinum-resistant ovarian cancer.

Colombo explained why the regimen’s success may hinge on its metronomic dosing strategy and discussed how the findings could influence future clinical decision-making for this challenging patient population.

Q: What do you believe were the key trial design elements or biological hypotheses that enabled this trial’s success where prior immunotherapy trials have failed?
Nicoletta Colombo, MD, PhD: Yeah, well, this is the $100 million question. I think it's difficult to say. I do believe it's probably related to the type of chemotherapy we used, which was metronomic administration with weekly paclitaxel.

There were studies in the past showing that metronomic administration of chemotherapy together with pembrolizumab and bevacizumab may lead to an improved outcome. So I believe that was probably the main reason why, in this study, we succeeded—where many others did not show any benefit.

In fact, there was 1 prior study from the AGO Study Group in Germany that was similar to ours, but in the control arm, they used not only weekly paclitaxel but also other drugs such as [pegylated liposomal doxorubicin] and topotecan. Overall, they could not demonstrate an advantage, but when looking at the subgroup of patients who received weekly paclitaxel, they saw a trend in favor of that regimen. Of course, the study was not powered enough to demonstrate a statistically significant difference, but the trend was very similar to ours. So I think there is more than one piece of evidence suggesting that weekly paclitaxel is the way to go if you want to use pembrolizumab and bevacizumab together.

Q: Given that the trial showed survival benefit in all comers, how might this change clinical decision-making for patients with platinum-resistant ovarian cancer? Do you foresee broader use of pembrolizumab in this setting, even for low PD-L1 expressers?
Colombo: Again, this is a very difficult question because it all depends on the approval by the authorities—you never know what they will decide.

If they decide that this drug should be approved only for PD-L1–positive patients, then, of course, we won’t be able to use it in the intention-to-treat population. On the other hand, as you said, the final overall survival analysis showed a statistically significant improvement even in the intention-to-treat population, so it would make sense to use it in all comers.

But again, we don’t know, and unfortunately, this depends on decisions by the FDA and, finally, the EMA. For me, given the results, I would be very happy to offer this regimen to all comers because it was very well tolerated and clearly showed incredible overall survival in this population.