Pembrolizumab plus olaparib maintenance improved progression-free survival in BRCA non-mutated ovarian cancer, with more toxicity

Design

Randomised, double-blind, placebo-controlled phase 3 trial, three arms

Population

1,367 women with stage III or IV BRCA non-mutated epithelial ovarian cancer

Primary outcome

Progression-free survival (PD-L1 CPS 10 or higher, then intention to treat)

Effect

Hazard ratio 0.66 (95% CI 0.53 to 0.83) in CPS 10 or higher; 0.71 (0.61 to 0.84) overall

KEYLYNK-001 was a randomised, double-blind, placebo-controlled phase 3 trial at 224 centres in 22 countries. It enrolled 1,367 women with stage III or IV epithelial ovarian, peritoneal or fallopian tube cancer without BRCA mutation, who had not received a PD-1 or PARP inhibitor. They were assigned 1:1:1 to chemotherapy plus pembrolizumab followed by pembrolizumab plus olaparib maintenance, chemotherapy plus pembrolizumab followed by pembrolizumab alone, or placebo throughout; bevacizumab was allowed at the investigator's discretion.

At the final analysis (median follow-up 49.6 months), progression-free survival with pembrolizumab plus olaparib versus control had a hazard ratio of 0.66 (95% CI 0.53 to 0.83) in the PD-L1 CPS 10 or higher population and 0.71 (0.61 to 0.84) in the whole intention-to-treat population. Pembrolizumab alone was not better than control in the CPS 10 or higher population (0.95, 0.77 to 1.19). Grade 3 or higher treatment-related adverse events occurred in 66%, 56% and 51% of the three groups; serious ones in 24%, 21% and 9%. Four women (1%) in the combination group died of treatment-related events.

The abstract does not report overall survival, and progression-free survival is a surrogate. The trial was funded by the manufacturer and enrolled mostly White participants. It supports the idea that the combination may have potential but it does not establish a new standard, and it was not tested against the established PARP-inhibitor options available in practice.

• Progression-free survival hazard ratio for the combination was 0.71 overall and 0.66 in CPS 10 or higher.
• Pembrolizumab without olaparib did not improve progression-free survival in the PD-L1-high population.
• Serious treatment-related adverse events were 24% with the combination against 9% with chemotherapy alone.
• Overall survival was not reported in the abstract, so weigh benefit against toxicity cautiously.

Why it matters

It tests a combination aimed at a group, BRCA non-mutated disease, that has few maintenance options.

Don't overread it

Progression-free survival is a surrogate for survival, and the added toxicity was substantial.

The statistics, in plain English

A progression-free survival hazard ratio of 0.71 means a 29% lower rate of progression or death at any time. It does not say the women lived longer; that depends on overall survival, which was not reported.

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