Pembrolizumab Plus Chemotherapy With/Without Bevacizumab Improves Survival Irrespective of PD-L1 Status in Ovarian Cancer

Pembrolizumab (Keytruda) and paclitaxel plus or minus bevacizumab significantly improved progression-free survival (PFS) and overall survival (OS) vs paclitaxel with or without bevacizumab alone, regardless of PD-L1 status, in patients with platinum-resistant ovarian cancer, according to data from the final analysis of the phase 3 KEYNOTE-B96 trial (NCT05116189).^1,2

The findings, which were presented for the first time during the 2026 European Society of Gynaecological Oncology Congress, showed that at a median follow-up of 32.7 months (range, 26.1-44.1), the median PFS in the pembrolizumab arm (n = 322) was 8.3 months (95% CI, 7.2-8.6) in the intention-to-treat (ITT) population vs 6.4 months (95% CI, 6.2-8.1) in the placebo arm (n = 321); this translated to a 27% reduction in the risk of disease progression or death (HR, 0.73; 95% CI, 0.62-0.87). The 12-month PFS rates in the respective arms were 33.7% and 22.5%, and the rates at 18 months were 17.3% and 9.0%, respectively.

In this population, the median OS with pembrolizumab was 17.7 months (95% CI, 15.2-19.2) vs 14.0 months (95% CI, 12.5-15.6) without pembrolizumab, which translated to an 18% reduction in death (HR, 0.82; 95% CI, 0.69-0.97; P = .0115). The 12-month OS rates in the pembrolizumab and placebo arms were 66.0% and 59.9%, respectively; the 18-month rates were 49.1% and 39.1%, respectively.

In the population of patients with a combined positive score (CPS) of at least 1, the median PFS with pembrolizumab (n = 234) was 8.3 months (95% CI, 7.0-9.5) vs 7.2 months (95% CI, 6.2-8.1) with placebo (n = 232), translating to a 24% reduction in the risk of disease progression or death (HR, 0.76; 95% CI, 0.62-0.93). The 12- and 18-month PFS rates with pembrolizumab in this population were 35.9% and 18.7%, respectively; with placebo, these rates were 23.9% and 10.5%, respectively. The median OS in the pembrolizumab arm was 18.2 months (95% CI, 15.3-21.3) vs 14.0 months (95% CI, 12.5-16.1) in the placebo arm; this translated to a 24% reduction in the risk of death (HR, 0.76; 95% CI, 0.62-0.93).

“This is the first phase 3 study to report a statistically significant improvement in OS in the CPS 1 or higher and ITT populations with an immune checkpoint inhibitor–based regimen in ovarian cancer,” the study authors shared in the presentation.¹ “The observed OS is among the longest reported in any clinical trial for platinum-resistant ovarian cancer, showing a clinically meaningful benefit of this regimen relative to the most standard-of-care [SOC] control arm, weekly paclitaxel with bevacizumab in bevacizumab-eligible patients.”

What was the design of KEYNOTE-B96?

The multicenter, double-blind, placebo-controlled, randomized KEYNOTE-B96 study enrolled patients with platinum-resistant, epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who previously received 1 or 2 lines of systemic therapy for ovarian carcinoma.³ To enroll, they were required to have received at least 1 line of platinum-based chemotherapy for ovarian cancer with radiographic evidence of disease progression within 6 months following the last dose.

Those with autoimmune disease that required systemic therapy within 2 years of treatment or a condition that needed immunosuppression were excluded, but those with previous exposure to anti–PD-(L)1 or PARP inhibition or bevacizumab were permitted.

Study participants (n = 643) were randomly assigned 1:1 to receive pembrolizumab at 400 mg or placebo every 6 weeks plus paclitaxel at 80 mg/m² with or without bevacizumab at 10 mg/kg. Randomization stratification factors included geographic region (US vs European Union vs rest of world), PD-L1 status (CPS < 1 vs CPS 1 to < 10 vs CPS ≥ 10), and investigator decision to use bevacizumab (yes vs no). Treatment with pembrolizumab continued until disease progression (PD) by RECIST 1.1 criteria, intolerable toxicity, or a maximum of 24 months. Patients were able to continue beyond PD if clinically stable and determined to be experiencing benefit per investigator assessment.

The primary end point was PFS by RECIST 1.1 criteria and investigator assessment.

What were the characteristics of patients enrolled in KEYNOTE-B96?

Of the 643 patients who underwent randomization, 72% had tumors with PD-L1 CPS of 1 or higher. The median patient age was 62 years (range, 37-85) with 38% of patients aged 65 or older. Most patients were White (67%), and slightly more than half (55%) had an ECOG performance status of 0. More than half of patients (73%) received bevacizumab. Regarding prior lines of therapy, 36% of patients had received 1 prior line and 64% had received 2; this treatment could have been bevacizumab (46%), a PARP inhibitor (39%), or a PD-(L)1 inhibitor (3%).

What earlier data were shared from KEYNOTE-B96?

At the time of the first interim analysis, the HR for PFS in the population of patients with a CPS of 1 or higher was 0.72 (95% CI, 0.58-0.89; P = .0014).¹ In the ITT population, the HR for PFS was 0.70 (95% CI, 0.58-0.84; P < .0001).

On February 10, 2026, the FDA approved pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) plus paclitaxel, with or without bevacizumab, for use in adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with a PD-L1 CPS of at least 1, as determined by an FDA-authorized test, and previous receipt of 1 or 2 systemic treatments.⁴ The decision was supported by prior KEYNOTE-B96 data.

It was also reported that the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion on the potential approval of pembrolizumab plus paclitaxel with or without bevacizumab for the same indication.²

What did the safety profile of the pembrolizumab regimen reveal?

The most common adverse effects experienced by at least 20% of patients included diarrhea (45%), fatigue (43%), nausea (41%), alopecia (38%), peripheral neuropathy (38%), epistaxis (31%), urinary tract infection (27%), constipation (25%), abdominal pain (24%), decreased appetite (24%), vomiting (24%), hypothyroidism (21%), cough (20%), hypertension (20%), and rash (20%).³

Moreover, the most frequent laboratory abnormalities that worsened from baseline and were reported in at least 20% of patients included anemia (85%), leukopenia (82%), decreased neutrophil count (71%), lymphopenia (60%), hypoalbuminemia (50%), hyponatremia (53%), hypomagnesemia (45%), increased aspartate aminotransferase level (43%), increased alanine aminotransferase level (40%), hypocalcemia (40%), increased alkaline phosphatase (31%), increased creatinine (29%), hypokalemia (27%), and neutropenia (21%).

What is the significance of the OS update from KEYNOTE-B96?

“The data support the use of pembrolizumab plus weekly paclitaxel, with or without bevacizumab, as a new SOC for patients with platinum-resistant ovarian cancer,” the study authors concluded.¹

References

1. Colombo N, Zsiros E, Sebastianelli A, et al. Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer: final analysis results from the randomized double-blind phase 3 ENGOT-ov65/KEYNOTE-B96 study. Abstract presented at: 2026 European Society of Gynaecological Oncology Congress; February 26-28, 2026; Copenhagen, Denmark. Abstract BO2-1 /526.
2. KEYTRUDA (pembrolizumab) plus paclitaxel with or without bevacizumab significantly improved key secondary end point of overall survival (OS) vs paclitaxel with or without bevacizumab in patients with platinum-resistant recurrent ovarian cancer. News release. Merck. February 27, 2026. Accessed March 2, 2026. https://www.merck.com/news/keytruda-pembrolizumab-plus-paclitaxel-with-or-without-bevacizumab-significantly-improved-key-secondary-endpoint-of-overall-survival-os-versus-paclitaxel-with-or-without-bevacizumab-in-patie/
3. Keytruda. Prescribing information; Merck Sharp & Dohme LLC; 2026. Accessed March 2, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/125514Orig1s186lbl.pdf
4. FDA approves pembrolizumab with paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. FDA. February 10, 2026. Accessed February 10, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-paclitaxel-platinum-resistant-epithelial-ovarian-fallopian-tube-or