Cytoreductive surgery and platinum-based chemotherapy are the standard of care for patients with newly diagnosed advanced ovarian cancer.1 However, approximately 75% of patients who have an initial response subsequently have a recurrence of their cancer, which is rarely curable.2 Here, Moore and colleagues present data from SOLO1, the first phase 3 trial in which patients with BRCA mutations and newly diagnosed advanced ovarian cancer received the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib as maintenance therapy after platinum-based chemotherapy.3
In this randomized, controlled, double-blind trial, eligible patients had newly diagnosed, International Federation of Gynecology and Obstetrics stage III to IV, high-grade serous or endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer; had received platinum-based chemotherapy; and were in clinical complete or partial response. Patients were randomized 2:1 to receive either 300-mg olaparib tablets twice daily or placebo. The primary end point was investigator-assessed progression-free survival (PFS) by modified Response Evaluation Criteria in Solid Tumors v1.1, with secondary end points including PFS, overall survival (OS), time from randomization to first subsequent therapy or death, and health-related quality of life using the Functional Assessment of Cancer Therapy-Ovarian Cancer score.
Of 391 randomized patients, 260 received olaparib and 131 received placebo. Baseline characteristics were well-balanced between the groups, and the median follow-up was 41 months. Patients received treatment for 2 years if there was no evidence of disease. Investigator-assessed PFS showed a significant 70% reduction in the risk for progression or death with olaparib versus placebo (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.23-0.41; P <.0001), which was similar to that of blinded independent central review (HR, 0.28; 95% CI, 0.20-0.39; P <.0001). Median time to first subsequent therapy or death was significantly longer for the olaparib group (between-group difference, 36.7 months; HR, 0.30; 95% CI, 0.22-0.40; P <.0001), as was the median time from randomization to second progression or death (between-group difference not calculable; HR, 0.50; 95% CI, 0.35-0.72; P <.0002). OS data are immature.
Adverse events in SOLO1 were mostly low grade. The most common high-grade (≥grade 3) toxicities associated with olaparib were anemia (22%) and neutropenia (8%). Olaparib dose reductions, interruptions, and discontinuations occurred in 28%, 52%, and 12%, respectively. No significant change from baseline in health-related quality of life scores with olaparib was observed.
These data are the first to show that maintenance olaparib leads to a substantial, unprecedented improvement in PFS in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation, with a difference of approximately 3 years in median PFS for olaparib versus placebo. There was also a statistically significant improvement with olaparib over placebo in time from randomization to a second progression event, suggesting that olaparib did not diminish patients’ ability to benefit from subsequent therapy. Olaparib was generally well-tolerated, with a safety profile consistent with that observed in the relapsed disease setting.
- Matulonis UA. Clin Adv Hematol Oncol. 2018;16(6):426-437.
- Hoppenot C, et al. Gynecol Oncol. 2018;148(1):204-212.
- Moore KN, et al. ESMO 2018. Abstract LBA7.