Among patients with platinum-resistant recurrent ovarian cancer (PRROC), the treatment combination of Keytruda (pembrolizumab) with weekly paclitaxel with or without Avastin (bevacizumab) was associated with significant improvements in progression-free survival (PFS) regardless of PD-L1 status and overall survival (OS), clinical trial results have shown.
Findings from the phase 3 ENGOT-ov65/KEYNOTE-B96 trial were shared at the European Society of Medical Oncology Congress 2025.
The analysis was broken down between the population of patients with a combined positive score (CPS) of 1 or higher and the intention-to-treat population. Furthermore, data were broken down between interim analysis 1 (IA1), which had a data cutoff date of April 3, 2024, and interim analysis 2 (IA2), which had a data cutoff date of May 5, 2025.
Glossary
- Progression-Free Survival (PFS): the length of time a patient lives with a disease without it getting worse or spreading.
- Overall Survival (OS): the length of time, usually measured from the start of diagnosis or treatment, that a patient is still alive.
- Combined Positive Score (CPS): a way to measure the amount of PD-L1 protein, which can affect treatment decisions, found on both cancer cells and certain immune cells in a tumor sample.
- Objective Response Rate (ORR): the percentage of patients whose cancer significantly shrinks or disappears after a specific treatment.
- Complete Response (CR): the disappearance of all signs of cancer following treatment, though it does not always mean the cancer is cured.
- Partial Response (PR): a decrease in the size or amount of cancer in the body by a specific amount, usually 30%, following treatment.
- Anemia: a condition where the body doesn't have enough healthy red blood cells to carry adequate oxygen to the body's tissues.
- Peripheral Neuropathy: nerve damage in the hands and feet that can cause symptoms like pain, tingling, numbness, or muscle weakness.
- Alopecia: the temporary or permanent loss of hair from the head or other parts of the body, often a side effect of chemotherapy or radiation.
- ECOG Performance Status: a scale, ranging from 0 (fully active) to 5 (dead), used by doctors to assess how a patient's disease is affecting their daily activities and physical well-being.
The CPS of 1 or Higher Population
At IA1, the median PFS was 8.3 months in the Keytruda arm compared with 7.2 months in the placebo arm, with 12-month PFS rates of 35.2% versus 22.6%, respectively.
At IA2, the median PFS was 8.3 months in the Keytruda arm compared with 7.2 months in the placebo arm; the 12-month PFS rates were 35.9% versus 23.9%, respectively, and the 18-month rates were 18.7% versus 10.5%.
The median OS was 18.2 months in the Keytruda arm compared with 14 months in the placebo arm, with 12-month OS rates of 69.1% versus 59.3%, and 18-month OS rates of 51.5% versus 38.9%, respectively.
The objective response rate (ORR) was 53% with a complete response (CR) rate of 9.9% and a partial response (PR) rate of 43.1%, in the Keytruda arm; in the placebo arm, the ORR was 46.6%, with a CR rate of 7.8% and a PR rate of 38.7%. The 12- and 18-month duration of response (DOR) rates in the Keytruda arm were 46.7% and 28.4% compared with 29.6% and 16.4% in the placebo arm.
The ITT Population
At IA1, the median PFS was 8.3 months with Keytruda compared with 6.4 months with placebo, with 12-month PFS rates of 33.1% and 21.3%, respectively.
At IA2, the median PFS was 8.3 months versus 6.4 months, respectively; the 12-month PFS rates were 33.7% versus 22.5%, and the 18-month PFS rates were 17.3% versus 9%.
The ORR was 50.4%, with a CR rate of 8.3% and a PR rate of 42%, in the Keytruda arm; in the placebo arm, the ORR was 40.8%, with a CR rate of 6% and a PR rate of 34.8%.Furthermore, the 12- and 18-month DOR rates in the Keytruda arm were 46.6% and 26.5% compared with 28.4% and 14.5% in the placebo arm.
“These data support the use of [Keytruda] plus weekly paclitaxel, with or without [Avastin], as a new standard of care for patients with PRROC,” presenting author Dr. Nicoletta Colombo of the Gynecologic Oncology Program at the European Institute of Oncology, IRCCS, in Milan, Italy, and the Department of Medicine and Surgery at the University of Milan-Bicocca in Italy, wrote with coauthors in the presentation.
Safety Analyses
Any-grade treatment-related side effects occurred in 97.8% of the Keytruda arm and 95.3% of the placebo arm; grade 3 (severe) or higher treatment-related side effects occurred in 67.5% and 55.3%, respectively. Treatment-related side effects were serious in 33.1% and 19.5%, led to death in 0.9% and 1.6%, and led to discontinuation of any treatment in 35.9% and 28%.
Any-grade immune-mediated side effects occurred in 39.1% and 18.9%, and grade 3 or higher events occurred in 11.6% and 3.5%. They were serious events in 10.9% and 2.2%, and led to treatment discontinuation in 6.9% and 2.5%.
The most common treatment-related side effects in both groups included anemia (49.7% versus 42.1%, respectively), peripheral neuropathy (38.8% versus 31.1%), alopecia (37.8% versus 34%), fatigue (35.3% versus 33%) and nausea (31.3% versus 27.4%). The most common immune-mediated side effects were hypothyroidism (17.8% versus 6%), infusion reactions (5.9% versus 4.7%) and hyperthyroidism (5% versus 0.6%).
Trial Breakdown
A total of 643 patients with histologically confirmed epithelial ovarian, fallopian tube or primary peritoneal carcinoma were enrolled in the trial and randomly assigned to either the Keytruda arm (322 patients) or the placebo arm (321 patients). Treatment was either Keytruda at 400 mg once every six weeks for 18 cycles or placebo on the same schedule; all patients received paclitaxel at 80 mg/m2 on days 1, 8, and 15 of each three-week-long cycle, and they either did or did not receive Avastin at 10 mg/kg every 2 weeks.
Patients were enrolled in the trial if they had received one or two prior lines of therapy with at least one platinum-based chemotherapy; prior anti-PD-1 or anti-PD-L1 agents, PARP inhibitors and Avastin were permitted. Additionally, patients had radiographic progression within six months after the last dose of platinum-based chemotherapy and an ECOG performance status of 0 or 1.
The median age of patients was 62 years versus 61 years in the Keytruda versus placebo arm, 64.3% and 67.6% of patients were White, 41.3% and 41.1% had a PD-L1 CPS from 1 to less than 10, and 31.4% and 31.2% had a PD-L1 CPS of at least 10.
Reference
- "Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer: Results from the randomized double-blind phase 3 ENGOT-ov65/KEYNOTE-B96 study," by Dr. Nicoletta Colombo. Presented at: European Society of Medical Oncology Congress 2025; October 17–20, 2025; Berlin, Germany. Abstract LBA3.
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