Two years of maintenance therapy with olaparib yielded “outstanding improvement” with regard to progression-free survival (PFS) compared with placebo in women with advanced ovarian cancer and a BRCA1 or BRCA2 mutation, according to a new study.
Newly diagnosed advanced ovarian cancer is generally treated with cytoreductive surgery and platinum-based chemotherapy, but most patients relapse within the first 3 years and the malignancy is largely not curable at that point. The new SOLO-1 trial was a phase III study examining whether the maintenance therapy with the PARP inhibitor olaparib can improve outcomes following platinum-based chemotherapy in this setting. The results were presented by Kathleen Moore, MD, of the Stephenson Cancer Center at the University of Oklahoma, at the European Society for Medical Oncology (ESMO) 2018 Congress, held October 19–23 in Munich.
The study included 391 patients with high-grade serous or endometrioid ovarian cancer; all were in clinical complete or partial response following chemotherapy. They were randomized 2:1 to receive either 2 years of olaparib maintenance therapy (260 patients) or placebo (131 patients), and the median follow-up period was 41 months.
The median PFS was 13.8 months with placebo, and the median was not yet reached with olaparib; Moore said the PFS with olaparib will likely be approximately 3 years longer than with placebo, and the hazard ratio (HR) for progression was 0.30 (95% CI, 0.23–0.41; P < .0001). A blinded independent central review of PFS yielded similar results.
A secondary endpoint, PFS2, defined as the time from randomization to the second progression event, was 41.9 months with placebo and again not yet reached with olaparib, for an HR of 0.50 (95% CI, 0.35–0.72; P = .0002). The time to first subsequent therapy or death was 14.1 months with placebo, and not yet reached with olaparib, for an HR of 0.30 (95% CI, 0.22–0.40; P < .0001).
Adverse events in the study were mostly low grade, with the most common grade 3 or higher events with olaparib including anemia (22%) and neutropenia (8%). Dose reductions of olaparib were required in 28% of patients, while interruptions and discontinuations were needed in 52% and 12%, respectively.
“The results of SOLO-1 herald a new era in treatment for women diagnosed with advanced ovarian cancer who carry a BRCA mutation,” Moore said, according to a press release. “This study demonstrates an outstanding improvement in PFS over placebo, which is maintained even after the olaparib is stopped at 2 years.”
Isabelle Ray-Coquard, MD, PhD, of the Université Claude Bernard Lyon Est, in Lyon, France, commented on the study, and agreed on the significance of the results. “The findings promise to change practice in this subgroup of patients with a BRCA mutation,” she said, adding that outstanding questions include whether this can be expanded to other high-grade serous or endometrioid ovarian cancer patients, and precisely what the ideal maintenance therapy in these patients will be. One ongoing study, the PAOLA-1 trial, is examining whether combining the PARP inhibitor with bevacizumab may improve results.