Pembrolizumab combined with olaparib improves PFS in BRCA wild-type ovarian cancer

Based on KEYLINK-001 released in2025 Data from the first interim analysis of the phase 3 trial (NCT03740165) of pembrolizumab in combination with chemotherapy, and maintenance pembrolizumab plus olaparib/olaparib, with or without bevacizumab

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<0.0001). At 36 months, the progression-free survival rates were 34.6% and 22.9%, respectively. The median follow-up time was 30.1 months. The final analysis, conducted in August 2024, showed that the median progression-free survival was 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). At 36 months, the median progression-free survival rates in the pembrolizumab/olaparib/olaparib group and the control group were 38.8% and 24.5%, respectively, and at 48 months they were 34.7% and 20.6%. The median follow-up time was 49.6 months.

In the intention-to-treat (ITT) population, significance was demonstrated for PD-L1 composite positivity scores (CPS) of less than 10 (HR, 0.71; 95% CI, 0.60-0.91) and 10 or greater (HR, 0.66; 95% CI, 0.53-0.83). In addition, significance was also shown in CPS in groups of 10 or more patients with bevacizumab (HR, 0.75; 95% CI, 0.53-1.06) or without bevacizumab (HR, 0.60; 95% CI, 0.44-0.82). For patients with a CPS of 10 or higher, the median PFS was 17.3 months in the pembrolizumab/olaparib group compared with 15.2 months in the control group (HR, 0.95; 95% CI, 0.77-1.19; P=0.3339). The PFS rates were 24.5% and 24.5% in the pembrolizumab/olaparib/olaparib and control groups at 36 months, and 21.1% and 20.6% at 48 months.

In theITT population, the median PFS was 15.2 months in the pembrolizumab/olaparib/olaparib group and 14.6 months in the control group (HR, 1.01; 95% CI, 0.87-1.18). At 36 months, the progression-free survival rates were 21.4% and 20.7% in the pembrolizumab/olaparib/olaparib group and 18.2% and 16.7% in the control group at 48 months. Likewise, in the final analysis, those with a CPS of less than 10 (HR, 1.01; 95% CI, 0.87-1.18) or 10 or greater (HR, 0.95; 95% CI, 0.77-1.19) did not show significance. and patients who received bevacizumab (HR, 1.22; 95% CI, 0.88-1.69) or who did not receive bevacizumab (HR, 0.76; 95% CI, 0.57-1.02).

At the time of final analysis,clinically meaningful improvements in PFS continued. The PFS benefit was generally consistent across prespecified subgroups. Because the PFS significance threshold for pembrolizumab versus control was not reached in the CPS 10 or above population, PFS and overall survival in the ITT population were not formally tested. A total of 1367 patients were randomly assigned in a 1:1:1 ratio to the control group (n=454), the pembrolizumab group (n=458), or the pembrolizumab plus olaparib group (n=455). The primary endpoint was investigator-assessed PFS according to RECIST v1.1, and the secondary endpoint was OS.

Median PFS among 10 or more CPS 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, median PFS for patients who did not receive bevacizumab was 13.7 months versus 10.1 months (HR, 0.66; 95% CI, 0.51-0.85).

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

OS was also performed without bevacizumab. For patients with a CPS of 10 or higher, 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, median OS was 43.6 months versus 37.3 months (HR, 0.85; 95% CI, 0.63-1.15). Additionally, for patients with a CPS of 10 or higher, median OS was not reached in the pembrolizumab group compared with 40.5 months in the control group (HR, 0.61; 95% CI, 0.38-0.98). For the ITT population, median OS was 44.5 months versus 37.3 months (HR, 0.80; 95% CI, 0.60-1.08).

The most common treatment-related adverse reactions (AEs) in the pembrolizumab/olaparib group, the pembrolizumab group, and the control group were anemia, nausea, and neutropenia. Immune-mediated adverse events include hypothyroidism, hyperthyroidism, and pneumonia.

Reference materials:https://www.onclive.com/view/pembrolizumab-plus-olaparib-improves-pfs-in-brca-wild-type-ovarian-cancer