Pembrolizumab/Chemo, Followed by Olaparib Maintenance, Boosts PFS in Advanced Ovarian Cancer

Frontline pembrolizumab (Keytruda) plus chemotherapy, followed by maintenance olaparib (Lynparza), with or without bevacizumab (Avastin), significantly improved progression-free survival (PFS) vs chemotherapy alone in patients with BRCA non-mutated advanced epithelial ovarian cancer, meeting the primary end point of the phase 3 KEYLYNK-001 trial (NCT03740165).1 However, the trial’s secondary end point of overall survival (OS) was not met.

The safety profiles of pembrolizumab and olaparib were consistent with those seen with the individual agents in previously reported trials, according to a news release.

These findings will be presented at a future medical meeting and presented to regulatory authorities.

“For people living with ovarian cancer, there remains an unmet need for new treatment options that have the potential to improve outcomes,” Gursel Aktan, MD, PhD, vice president of global clinical development at Merck Research Laboratories, stated in a news release. “KEYLYNK-001 is the first positive phase 3 trial for [pembrolizumab] plus [olaparib], highlighting our commitment to research that may help address the global impact of women’s cancers.”

The randomized, double-blind KEYLYNK-001 trial enrolled patients at least 18 years of age with histologically confirmed, FIGO stage III or IV epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.2 Patients must have recently undergone primary debulking surgery, been eligible for primary debulking surgery, or been a potential candidate for interval debulking surgery. Patients must have been eligible to receive carboplatin and paclitaxel, and an ECOG performance status of 0 or 1 was also required. Patients needed to be able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing for BRCA1/2 and PD-L1 status prior to random assignment.

Patients were excluded if they had mucinous, germ cell, or borderline ovarian tumors; a known or suspected deleterious germline or somatic BRCA1/2 mutation; a history of non-infectious pneumonitis requiring steroids or current pneumonitis; myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), or features suggestive of MDS/AML; or known active central nervous system metastases and/or carcinomatous meningitis. Patients with brain metastases were allowed to enroll if they were previously treated and stable.

Prior treatment for any stage of ovarian cancer, including radiation or systemic anticancer therapy, was not allowed. Any prior therapy with an anti–PD-1, –PD-L1, or –PD-L2 agent, or any agent directed to another stimulatory or co-inhibitory T-cell receptor, was not allowed, and prior PARP inhibitor therapy was not permitted.

The trial included 1367 patients who were randomly assigned to receive intravenous pembrolizumab at 200 mg plus paclitaxel and carboplatin every 3 weeks for 5 cycles, followed by pembrolizumab at the same dose level for approximately 2 years plus oral olaparib at 300 mg twice daily; pembrolizumab and chemotherapy at the same doses for 5 cycles, followed by pembrolizumab and oral placebo; or chemotherapy plus placebo.1

All patients were allowed to receive bevacizumab at investigator discretion. Patients who needed to discontinue paclitaxel due to hypersensitivity or an adverse effect were allowed to receive docetaxel plus carboplatin.

The primary end point was investigator-assessed PFS per RECIST 1.1 criteria in patients with a PD-L1 combined positive score of at least 10 and in all patients.1,2 Secondary end points included OS in all patients and in those with PD-L1–positive tumors, PFS per blinded independent central review in all patients and in patients with PD-L1–positive tumors, time to second progression, safety, and quality of life.2

References

1. Merck announces phase 3 KEYLYNK-001 trial met primary endpoint of progression-free survival (PFS) in patients with advanced epithelial ovarian cancer. News release. Merck. December 9, 2024. Accessed December 9, 2024. https://www.merck.com/news/merck-announces-phase-3-keylynk-001-trial-met-primary-endpoint-of-progression-free-survival-pfs-in-patients-with-advanced-epithelial-ovarian-cancer/
2. Study of chemotherapy with pembrolizumab (MK-3475) followed by maintenance with plaparib (MK-7339) for the first-line treatment of women with BRCA non-mutated advanced epithelial ovarian cancer (EOC) (MK-7339-001/​KEYLYNK-001/​ENGOT-ov43/​GOG-3036). ClinicalTrials.gov. Updated November 19, 2024. Accessed December 9, 2024. https://clinicaltrials.gov/study/NCT03740165