PEMBROLIZUMAB combined with chemotherapy followed by maintenance pembrolizumab and olaparib significantly prolonged progression-free survival in patients with newly diagnosed advanced BRCA non-mutated ovarian cancer, according to Phase III findings.
The ENGOT-OV43/GOG-3036/KEYLYNK-001 trial involved 1,367 patients with stage III–IV epithelial ovarian, primary peritoneal, or fallopian tube cancer without a BRCA1/2 mutation. The combination reduced the risk of disease progression or death compared with chemotherapy-based control treatment.
Olaparib, a PARP inhibitor, is established as first-line maintenance treatment for some patients with BRCA-mutated ovarian cancer. Researchers investigated whether combining PARP inhibition with pembrolizumab could also improve outcomes among patients without BRCA mutations.
The randomised, double-blind Phase III trial was conducted across 224 gynaecological oncology centres in 22 countries.
After one lead-in chemotherapy cycle, participants were randomly assigned to pembrolizumab plus chemotherapy followed by pembrolizumab–olaparib maintenance; pembrolizumab plus chemotherapy followed by pembrolizumab–placebo maintenance; or a control regimen of placebo plus chemotherapy followed by placebo maintenance. Bevacizumab could also be administered at investigators’ discretion.
The median participant age was 61 years, and all participants were female.
At the first interim analysis, after a median follow-up of 30.1 months, pembrolizumab–olaparib significantly improved progression-free survival among patients with a PD-L1 combined positive score (CPS) of at least 10.
Compared with the control group, the combination was associated with a 37% lower risk of progression or death in this population (HR: 0.63; 95% CI: 0.49–0.80; p<0.0001).
Across the overall intention-to-treat population, the risk was reduced by 32% (HR: 0.68; 95% CI: 0.58–0.81; p<0.0001).
The benefit remained at the final analysis, after median follow-up reached 49.6 months. The HR was 0.66 among patients with CPS ≥10 and 0.71 across the intention-to-treat population.
Pembrolizumab without olaparib did not significantly improve progression-free survival in the CPS ≥10 population compared with control (HR: 0.95; 95% CI: 0.77–1.19; p=0.33).
Grade 3 or worse treatment-related adverse events occurred in 66% of patients receiving pembrolizumab–olaparib, compared with 56% receiving pembrolizumab and 51% in the control group.
The most common severe events included neutropenia and anaemia. Serious treatment-related adverse events occurred in 24%, 21%, and 9% of patients, respectively.
Four treatment-related deaths occurred in the pembrolizumab–olaparib group and one in the pembrolizumab group.
The investigators concluded that the combination could represent a potential first-line approach for BRCA non-mutated advanced epithelial ovarian cancer, although its increased toxicity remains important when interpreting the benefit.
Reference
Garcia-Donas J et al. Chemotherapy with or without pembrolizumab followed by maintenance pembrolizumab with or without olaparib as first-line treatment of patients with advanced BRCA non-mutated epithelial ovarian cancer (ENGOT-OV43/GOG-3036/KEYLYNK-001): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2026. doi:10.1016/S1470-2045(26)00223-8.
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