Olaparib improves survival outcomes for patients with germline BRCA-mutated, platinum-sensitive, relapsed ovarian cancer who received at least two prior lines of platinum-based chemotherapy, according to a comparative effectiveness study.
A prior phase III study showed activity of olaparib in patients with germline BRCA-mutated, platinum-resistant or partially platinum-sensitive, relapsed ovarian cancer.
Richard T Penson, MD, MRCP, Harvard Medical School and Massachusetts General Hospital, and colleagues conducted a phase III trial (SOLO3) of olaparib vs nonplatinum chemotherapy in patients with germline BRCA-mutated, platinum-sensitive, relapsed ovarian cancer who had received at least two prior lines of platinum-based chemotherapy. The open-label trial randomized (2:1) 266 patients to olaparib (300 mg twice daily; n = 178) or physician’s choice of single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan; n = 88).
The primary endpoint of SOLO3 was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review. A key secondary endpoint was progression-free survival (PFS) assessed by blinded independent central review in the intention-to-treat population.
Results of the study were published in the Journal of Clinical Oncology (April 2020;38[11]:1164-1174).
Among patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the ORR was significantly higher with olaparib compared with chemotherapy (72.2% vs 51.4%, respectively; OR, 2.53; 95% CI, 1.40-4.58; P = .002).
A subgroup analysis of ORR in patients who had received two prior lines of treatment also favored the olaparib cohort (84.6% vs 61.5%, respectively; OR, 3.44; 95% CI, 1.42-8.54).
Furthermore, PFS significantly favored the olaparib cohort (13.4 vs 9.2 months, respectively; HR, 0.62; 95% CI, 0.43-0.91; P = .013).
Adverse events were consistent with the established safety profiles of olaparib and chemotherapy, Dr Penson and colleagues noted.
In their concluding remarks, authors of the study wrote that, “Olaparib results in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a germline BRCA mutation who had received at least two prior lines of platinum-based chemotherapy.”—Zachary Bessette
