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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Tuesday, January 21, 2025
The use of olaparib did not improve overall survival compared with nonplatinum chemotherapy in patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer and in patients with three or more previous lines of chemotherapy, according to an update from the phase III SOLO3 trial. In fact, the PARP inhibitor even seemed detrimental to overall survival in this patient population. The research was conducted by Richard T. Penson, MD, MRCP, of Massachusetts General Hospital, Boston, and published in the Journal of Clinical Oncology.
“On the basis of these results, olaparib as a line of treatment indication for germline BRCA-mutated ovarian cancer after at least three previous chemotherapy lines has been voluntarily withdrawn,” the investigators commented.
The open-label trial included 266 patients randomly assigned on a 2:1 basis to receive oral olaparib (300 mg, twice daily) or a single-agent nonplatinum chemotherapy of the physician’s choice (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). A total of 25% of patients in the chemotherapy arm withdrew before death, compared with 10.7% of patients in the olaparib arm.
The study authors noted that previous results indicated that olaparib significantly improved the objective response rate (the primary endpoint) and progression-free survival vs nonplatinum chemotherapy. Overall survival was the prespecified secondary endpoint.
Overall survival was similar with olaparib (median = 34.9 months) and nonplatinum chemotherapy (median = 32.9 months), with a hazard ratio of 1.07. In patients with two previous chemotherapy lines, overall survival was longer with olaparib (37.9 months) than with chemotherapy (28.8 months), with a hazard ratio of 0.83. By contrast, in patients with three or more previous chemotherapy lines, overall survival was worse in the olaparib arm (29.9 months) than in the chemotherapy arm (39.4 months), with a hazard ratio of 1.33.
Of note, none of the six patients in the olaparib arm with a BRCA reversion mutation achieved an objective tumor response. This subgroup is small, but the authors theorized that BRCA reversion mutations may confer resistance to olaparib.
Disclosure: For full disclosures of the study authors, visit ascopubs.com.
