This FDA confirmatory phase III study evaluated olaparib vs treatment of physician’s choice in BRCA-mutated, platinum-sensitive relapsed ovarian cancer.
Patients with BRCA-mutated, platinum-sensitive relapsed ovarian cancer derived significant clinical benefit from treatment with olaparib monotherapy compared with treatment of physician’s choice, according to the results of the SOLO3 trial, a US Food and Drug Administration (FDA) confirmatory phase III study (abstract 5506). The data were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
Olaparib gained FDA accelerated approval based on the results of a pooled analysis of phase I and II data in patients with advanced BRCA-mutated ovarian cancer who had received 3 or more prior lines of therapy. In this early data, patients had a 34% overall response rate. Accelerated approvals are supposed to be contingent on results of confirmatory trials showing clinical benefit of the treatment.
“SOLO3 provides important prospective data on the efficacy of these treatment options for women with heavily pre-treated platinum sensitive recurrent BRCA-mutated ovarian cancer,” said Richard T. Penson, MD, of Massachusetts General Hospital, who presented the updated results at the meeting.
The study randomly assigned patients 2:1 to olaparib (n = 178) or treatment of physician’s choice, which included paclitaxel, topotecan, gemcitabine, or pegylated liposomal doxorubicin. The primary endpoint was overall response rate.
Overall response rate for olaparib was 72% as measured by blinded Independent Review Committee, with 9% of patients achieving complete remission. In the chemotherapy arm, the overall response rate was 51%, with 3% of patients achieving complete remission (odds ratio, 2.53; 95% CI, 1.40–4.58; P = .002).
In addition to a significantly improved overall response rate, assignment to olaparib resulted in a 38% decreased risk for progression as assessed by blinded independent ventral review compared with physician’s choice (hazard ratio, 0.62; 95% CI, 0.43–0.91).
Median progression-free survival improved by about 4 months among patients assigned to olaparib (median 13.4 vs 9.2 months; P = .013) compared with physician’s choice. Investigator review yielded a similar difference (13.2 vs 8.5 months; P < .001).
Overall survival data are still immature.
“Subsequent therapies clearly are important and likely to dilute out any overall survival advantage for effective biological therapies,” Penson said. “Seventy participants in the olaparib arm (39%) and 29 in the chemotherapy arm-a third-received platinum immediately or as a subsequent line of therapy.”
Additionally, 3% of patients in olaparib group and 27% in the chemotherapy arm received a PARP inhibitor as part of their first or second subsequent therapy.
There was no clinically or statistically significant difference in health-related quality of life between the olaparib and chemotherapy arms. Serious adverse events were reported in 24% of patients assigned to olaparib and 18% of patients assigned to physician’s choice. However, there were half as many adverse events leading to treatment discontinuation in the olaparib arm.
In total, 4 participants (2%) assigned to olaparib and 3 assigned to chemotherapy (4%) developed myelodysplastic syndrome/acute myeloid leukemia. Also, 3 patients in the olaparib arm were diagnosed with new primary malignancy: BRCA2-mutated lung cancer, BRCA1-mutated gastric cancer, and BRCA1-mutated breast cancer.
Abstract discussant Don S. Dizon, MD, FACP, FASCO, of Lifespan Cancer Institute, said that a question posed by many looking at these results might be, “Do we need chemotherapy to treat recurrence?” The answer is, “Probably not,” he said.
However, he did point out that in SOLO3, women with platinum-sensitive disease were not treated with a platinum regimen in the control arm. Additionally, toxicities seen here were not ones commonly seen in previous randomized trials, with a higher serious adverse event rate.