Olaparib confers ‘unprecedented’ PFS benefit in ovarian cancer
MUNICH — Maintenance olaparib significantly improved PFS among women with advanced ovarian cancer who harbored BRCA1 or BRCA2 mutations, according to results of the randomized phase 3 SOLO1 trial presented at European Society of Medical Oncology Congress.
Median PFS among women who received olaparib (Lynparza; AstraZeneca Merck) was nearly 3 years longer than that achieved by women who received placebo.
Study author Kathleen Moore, MD, associate professor at Stephenson Cancer Center at University of Oklahoma, described the improvement as “substantial and unprecedented.”
“We believe the SOLO1 data really promise a change in the standard of care for women with advanced ovarian cancer who harbor a BRCA mutation, and we hope this will be available to patients relatively soon,” Moore said during a press conference.
Women with newly diagnosed ovarian cancer typically undergo cytoreductive surgery and platinum-based chemotherapy. The majority of them relapse within 3 years and undergo additional chemotherapy; however, they are largely uncurable after relapse.
“The percentage of patients who survive disease free for long periods of time is dismally low, hovering in the 10% to 15% range,” Moore said. “If we are going to make meaningful improvements on that rate, it has to be in frontline treatment.”
The prospective, international, double-blind SOLO1 trial evaluated maintenance therapy with the PARP inhibitor olaparib for women who underwent platinum chemotherapy for newly diagnosed BRCA-positive ovarian cancer.
The double-blind trial included 390 patients with stage III to stage IV high-grade serous or endometrioid ovarian, primary peritoneal or fallopian tube cancer. All women harbored BRCA mutations and were in clinical complete or partial response after platinum-based chemotherapy.
Researchers randomly assigned 260 patients to 300 mg olaparib twice daily. The other 130 patients received placebo. Treatment continued until disease progression or for a maximum 2 years. Women with stable disease at 2 years had an opportunity to remain on treatment after discussions with their medical team.
Baseline characteristics were balanced between groups.
Investigator-assessed PFS served as the primary endpoint.
Median follow-up was 41 months.
Investigator-assessed PFS, performed at 51% maturity, showed olaparib reduced the risk for progression or death by 70% compared with placebo (median, not reached vs. 13.8 months; HR = 0.3; 95% CI, 0.23-0.41).
Blinded independent central review-assessed PFS, performed at 38% maturity, yielded a similar result (median, not reached vs. 14.1 months; HR = 0.28; 95% CI, 0.2-0.39).
“There was no obvious change in Kaplan-Meier curves after 2 years in the olaparib group, indicating an apparent enduring treatment benefit after stopping treatment,” Moore said.
Olaparib-treated patients also achieved longer time to first subsequent therapy or death (median, 51.8 months vs. 15.1 months; HR = 0.3; 95% CI, 0.22-0.4), as well as longer time from randomization to second progression or death (median, not reached vs. 41.9 months; HR = 0.5; 95% CI, 0.35-0.72).
“[This indicates] olaparib did not diminish patients’ ability to benefit from subsequent therapy,” Moore said.
OS data are immature.
Olaparib appeared well tolerated, exhibiting a safety profile consistent with what has been observed in the relapsed setting.
Most adverse events were low grade, according to researchers. The most common grade 3 or higher toxicities observed among olaparib-treated patients were anemia (22%) and neutropenia (8%).
Twenty-eight percent of patients assigned olaparib required dose reductions, 52% required dose interruptions and 12% discontinued therapy.
Researchers reported no change in baseline health-related quality-of-life scores with olaparib. – Mark Leiser
Moore KN, et al. Abstract LBA7_PR. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.
Disclosures: AstraZeneca provided funding for this study. Moore reports fees for advisory board roles with AstraZeneca, Advaxis, Clovis, Genentech/Roche, Immunogen, Janssen, Tesaro and VBL Therapeutics. Please see the abstract for all other authors’ relevant financial disclosures.