Pembrolizumab Combinations Show Survival Benefits in Bladder and Ovarian Cancers

Two major clinical trials have demonstrated significant survival benefits for pembrolizumab-based combination regimens in treating bladder and ovarian cancers, with one regimen receiving FDA approval in February 2026.

The KEYNOTE-B15 study randomized 808 patients with muscle-invasive bladder cancer to receive either perioperative enfortumab vedotin plus pembrolizumab or neoadjuvant cisplatin-based chemotherapy, both given with surgery. The study used event-free survival as the primary endpoint. A substantial reduction in recurrence or progression risk was observed with enfortumab vedotin plus pembrolizumab, alongside a statistically significant overall survival advantage. The combination of enfortumab vedotin, an antibody-drug conjugate, with pembrolizumab, an immune checkpoint inhibitor, has become the standard treatment for metastatic bladder cancer in recent years.

Cisplatin-based chemotherapy given for about three months before surgery has been the standard of care for muscle-invasive bladder cancer for about 25 years. In the KEYNOTE-B15 study, there was no difference in the ability to proceed with surgery on either arm of the study, and no clear increase in complications was observed.

In platinum-resistant ovarian cancer, the phase 3 KEYNOTE-B96 trial showed that pembrolizumab plus paclitaxel with or without bevacizumab is the first PD-1 inhibitor-based regimen to demonstrate a statistically significant improvement in overall survival regardless of PD-L1 status. At the final analysis, after a median follow-up of 32.7 months (range, 26.1-44.1), the pembrolizumab regimen demonstrated a statistically significant and clinically meaningful improvement in overall survival.

On February 10, 2026, the FDA approved pembrolizumab and pembrolizumab and berahyaluronidase alfa-pmph in combination with paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. The European Medicines Agency's Committee for Medicinal Products for Human Use adopted a positive opinion recommending approval of pembrolizumab in combination with paclitaxel with or without bevacizumab for the treatment of platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal carcinoma in adults whose tumors express PD-L1 (CPS ≥1), and who have received one or two prior systemic treatment regimens.

In the all comers population of KEYNOTE-B96, pembrolizumab plus paclitaxel with or without bevacizumab reduced the risk of disease progression or death by 27% (HR=0.73 [95% CI, 0.62-0.87]) compared to paclitaxel with or without bevacizumab alone. In patients with platinum-resistant recurrent ovarian cancer whose tumors express PD-L1 (CPS ≥1), the pembrolizumab regimen reduced the risk of disease progression or death by 24% (HR=0.76 [95% CI, 0.62-0.93]) versus paclitaxel with or without bevacizumab alone. The pembrolizumab regimen also demonstrated a clinically meaningful improvement in overall survival in patients with platinum-resistant recurrent ovarian cancer whose tumors express PD-L1 (CPS ≥1), reducing the risk of death by 24% (HR=0.76 [95% CI, 0.62-0.93]) compared to paclitaxel with or without bevacizumab.

The safety profile of pembrolizumab in the KEYNOTE-B96 trial was consistent with that observed in previously reported studies; no new safety concerns were identified. Grade ≥3 treatment-related adverse events occurred in 67.8% of patients receiving the pembrolizumab regimen (n=320) versus 55.3% of patients receiving the placebo regimen (n=318). Treatment-related adverse events led to death in 1.3% of patients receiving the pembrolizumab regimen and 1.6% of patients receiving the placebo regimen.

Immune-mediated adverse events and infusion reactions of any grade occurred in 39.4% of patients receiving the pembrolizumab regimen and 18.9% of patients receiving the placebo regimen. The most common of these events (occurring in ≥10% of patients) was hypothyroidism (18.1%) in patients receiving the pembrolizumab regimen. Immune-mediated adverse events led to death in 0.6% of patients in the pembrolizumab arm and in no patients in the placebo arm.

Ovarian cancer is the eighth most commonly diagnosed cancer and the eighth leading cause of cancer death among women worldwide. As of 2022, there were more than 324,000 patients diagnosed with ovarian cancer and almost 207,000 deaths from the disease globally. Over 80% of patients diagnosed with ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens. Of these patients, approximately 25% will experience disease progression within six months of completing first-line platinum-based chemotherapy, defined as primary platinum-resistant ovarian cancer. Prognosis is particularly poor for these patients and approved treatment options are limited.

KEYNOTE-B96, also known as ENGOT-ov65, is a multicenter, randomized, double-blind placebo-controlled Phase 3 trial (ClinicalTrials.gov, NCT05116189). Two patients who participated in the KEYNOTE-B96 trial both had platinum-resistant ovarian cancer with progression within 3 months after the last platinum exposure. Both patients had no evidence of disease after 3 to 4 months of weekly paclitaxel with the combination. They ultimately stopped the weekly paclitaxel because of adverse effects but continued for an additional several months of maintenance with pembrolizumab or placebo plus bevacizumab. Both patients still had no evidence of disease 18 months after coming off the KEYNOTE-B96 clinical trial.