Pembrolizumab/Olaparib Yields PFS Significance in Advanced Ovarian Cancer

The KEYLYNK-001 trial found improved PFS among patients with advanced ovarian cancer given pembrolizumab/olaparib.

A statistically significant and clinically meaningful improvement in progression-free survival (PFS) was noted when pembrolizumab (Keytruda) was combined with chemotherapy followed by maintenance plus pembrolizumab plus olaparib (Lynparza) with or without bevacizumab (Avastin) for patients with advanced BRCA non-mutated epithelial ovarian cancer, according to results from the first interim analysis of the phase 3 KEYLYNK-001 trial (NCT03740165).

Results were presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO). The median PFS was 23.7 months in the pembrolizumab/olaparib group and 15.2 months in the control group (HR, 0.63; 95% CI, 0.49-0.80; P <.0001) for patients with a combined positive score (CPS) of 10 or more. At 36 months, the PFS rates were 34.6% vs 22.9%, respectively. The median follow-up was 30.1 months.

The final analysis conducted in August 2024 had a median PFS of 23.9 months in the pembrolizumab/olaparib group and 15.2 months in the control group (HR, 0.66; 95% CI, 0.53-0.83) for those with a CPS of 10 or more. At 36 months, the median PFS rates were 38.8% vs 24.5%, and at 48 months they were 34.7% vs 20.6% in the pembrolizumab/olaparib and control arms, respectively. The median follow-up was 49.6 months.

In the intent-to-treat (ITT) population, PD-L1 with a CPS of less than 10 (HR, 0.71; 95% CI, 0.60-0.91) and 10 or more (HR, 0.66; 95% CI, 0.53-0.83) both showed significance. Additionally, in the CPS of 10 or more population, bevacizumab use (HR, 0.75; 95% CI, 0.53-1.06), or no bevacizumab use (HR, 0.60; 95% CI, 0.44-0.82) showed significance as well.

For those with a CPS of 10 or more, the median PFS was 17.3 months in the pembrolizumab arm vs 15.2 months in the control group (HR, 0.95; 95% CI, 0.77-1.19; P = .3339). At 36 months, the PFS rates were 24.5% vs 24.5% and at 48 months they were 21.1% vs 20.6% in the pembrolizumab and control arms, respectively.

In the ITT population, the median PFS was 15.2 months in the pembrolizumab arm and 14.6 months in the control arm (HR, 1.01; 95% CI, 0.87-1.18). At 36 months, the PFS rates were 21.4% vs 20.7% and at 48 months 18.2% vs 16.7% in the pembrolizumab and control arms, respectively.

At final analysis, those with a CPS of less than 10 (HR, 1.01; 95% CI, 0.87-1.18) or 10 or more (HR, 0.95; 95% CI, 0.77-1.19) did not show significance. As well as patients who received bevacizumab (HR, 1.22; 95% CI, 0.88-1.69) or did not (HR, 0.76; 95% CI, 0.57-1.02).

“The clinically meaningful improvement in PFS continued at final analysis. The PFS benefit was generally consistent across prespecified subgroups,” Matthew Powell, MD, a gynecologic oncology surgeon from Siteman Cancer Institute stated during the presentation. “Since PFS significance threshold of pembrolizumab vs control in the CPS 10 or more population was not met, formal testing of PFS in the ITT population and overall survival was not performed.”

A total of 1367 patients were randomly assigned 1:1:1 to either the control group (n = 454), pembrolizumab group (n = 458), or the pembrolizumab plus olaparib group (n = 455).

In the control group, 6 cycles of carboplatin/paclitaxel were given followed by olaparib placebo maintenance given twice daily for up to 2 years from cycle 7 onward; every 3 weeks for up to 35 cycles, pembrolizumab placebo maintenance could be given with or without bevacizumab.

In the pembrolizumab group, 6 cycles of carboplatin/paclitaxel were given followed by olaparib placebo maintenance twice daily for up to 2 years from cycle 7 onward; 200 mg of pembrolizumab was given every 3 weeks for up to 35 cycles with or without bevacizumab.

In the pembrolizumab/olaparib group, 6 cycles of carboplatin/paclitaxel were given followed by 300 mg of olaparib twice daily for up to 2 years; pembrolizumab was given every 3 weeks for up to 35 cycles with or without bevacizumab.

The primary end point was PFS assessed by the investigator per RECIST v1.1, and the secondary end point was OS.

Across all groups, the median age was 61 years old, a majority of patients were White, and the primary cancer was ovarian epithelioid. In the pembrolizumab/olaparib group, 85.5% had high grade serous histology, as well as 86.9% in the pembrolizumab group, and 84.4% in the control group; followed by 6.2%, 5.5%, and 6.2% with clear cell; and 4.4%, 2.4%, and 3.3% had endometrioid.

Regarding surgery, 20.2% of patients in the pembrolizumab/olaparib group had R0 primary debulking, 21.4% in the pembrolizumab group, and 20.5% in the control group; R1 primary debulking was noted in 34.1%, 33.0%, and 33.3%; interval debulking occurred in 36.5%, 38.0%, and 37.4%; while no surgery was noted in 9.2%, 7.6%, and 8.8%. Bevacizumab use was found in 43.7%, 44.8%, and 45.4%; while it was not used in 56.3%, 55.2%, and 54.6% of patients in the 3 groups, respectively.

The median PFS for the CPS of 10 or more who did not receive bevacizumab was 16.4 months in the pembrolizumab/olaparib group and 10.2 months in the control group (HR, 0.56; 95% CI, 0.38-0.84). In the ITT population, the median PFS in those who did not receive bevacizumab was 13.7 months vs 10.1 months (HR, 0.66; 95% CI, 0.51-0.85).

Similarly in the same populations, the median PFS for those in the pembrolizumab group was 15.9 months vs 10.2 months in the control group (HR, 0.53; 95% CI, 0.36-0.79) for those with a CPS of 10 or more and did not receive bevacizumab. In the ITT population, the median PFS was 11.9 months vs 10.1 months (HR, 0.69; 95% CI, 0.53-0.90) for those who did not receive bevacizumab.

OS was also conducted without bevacizumab as well. For those with a CPS of 10 or more, the median OS was 44.6 months in the pembrolizumab/olaparib group and 40.5 months in the control group (HR, 0.93; 95% CI, 0.60-1.45). In the ITT population, the median OS was 43.6 months vs 37.3 months (HR, 0.85; 95% CI, 0.63-1.15).

Additionally, the median OS was not reached in the pembrolizumab group vs 40.5 months in the control group (HR, 0.61; 95% CI, 0.38-0.98) in those with a CPS of 10 or more. For the ITT population, the median OS was 44.5 months vs 37.3 months (HR, 0.80; 95% CI, 0.60-1.08).

The most common treatment related adverse effects (AEs) across the pembrolizumab/olaparib group, the pembrolizumab group, and the control groups were anemia (54.9% vs 41.2% vs 41.0%), nausea (44.9% vs 34.4%, vs 27.8%), and neutropenia (35.6% vs 28.5% vs 29.7%). Immune-mediated AEs included hypothyroidism (20.1% vs 20.6% vs 9.3%), hyperthyroidism (7.5% vs 9.6% vs 5.1%), and pneumonitis (3.8% vs 3.7% vs 0.4%).

Reference

Powell M. Chemotherapy with or without pembrolizumab followed by maintenance with olaparib or placebo for first-line treatment of advanced BRCA non-mutated epithelial ovarian cancer:Results from the randomized phase 3 ENGOT-OV43/GOG-30. Presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO); Seattle, WA, March 14-17, 2025.