Maintenance olaparib extends OS among women with BRCA-mutated relapsed ovarian cancer
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Maintenance therapy with olaparib extended OS compared with placebo among women with platinum-sensitive, BRCA-mutated relapsed ovarian cancer, according to the final analysis of the randomized phase 3 SOLO-2 study scheduled for presentation during the ASCO20 Virtual Scientific Program.
Researchers reported median OS of more than 51 months among women assigned olaparib (Lynparza; AstraZeneca, Merck) and more than 38 months among those assigned placebo.
The findings establish olaparib as standard maintenance treatment for women with BRCA-related relapsed ovarian cancer who respond to platinum-based chemotherapy, Andres Poveda, MD, gynecologic cancer and sarcoma specialist at Initia Oncology at Hospital Quirónsalud in Spain, and colleagues concluded.
“A median OS improvement of nearly 13 months is impressive in ovarian cancer and brings a substantial benefit to our patients,” Poveda said in a press release. “With the addition of OS data, this study helps usher in a new era of personalized medicine for women with this difficult-to-treat cancer.”
Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for treatment of specific patients with gynecologic, breast or pancreatic cancers.
BRCA mutations are well-established targets for PARP inhibitors, and the unique mechanism of this class of agents illustrates the potential of targeted therapies for specific gene mutations, researchers wrote.
Previously released results of the double-blind, multicenter SOLO-2 trial helped support approval of olaparib maintenance for women with platinum-sensitive, relapsed ovarian cancer who harbor BRCA mutations.
The trial included 295 women with recurrent germline BRCA-positive ovarian, fallopian tube or primary peritoneal cancer who had received at least two prior lines of treatment and were in response to their most recent platinum-based chemotherapy.
Researchers assigned women 2:1 to olaparib tablets at a dose of 300 mg twice daily or placebo.
Investigator-assessed PFS served as the primary endpoint. OS served as a key secondary endpoint.
A higher percentage of women assigned olaparib had at least 5 years cumulative exposure to their assigned treatment (22.1% vs. 9.1%).
As Healio previously reported, results showed significantly longer median PFS with olaparib than placebo (19.1 months vs. 5.5 months; HR = 0.3; 95% CI, 0.22-0.41).
In their ASCO abstract, Poveda and colleagues provided final OS results, the first for a PARP inhibitor for this patient population.
Median follow-up was 65 months in each treatment group.
At that time, a higher percentage of women assigned olaparib than placebo remained alive and had not received subsequent treatment (28.3% vs. 12.8%). More than one-third (38.4%) of women assigned placebo crossed over to olaparib treatment.
Analysis of the entire cohort showed median OS of 51.7 months among women assigned olaparib and 38.8 months among those assigned placebo (HR = 0.74; 95% CI, 0.54-1).
Researchers also performed a preplanned OS sensitivity analysis to assess olaparib’s effect on women found to have germline BRCA mutations as determined by the BRACAnalysis test (Myriad Genetics). In this group, results showed a more pronounced OS benefit with olaparib compared with placebo (median, 52.4 months vs. 37.4 months; HR = 0.71; 95% CI, 0.52-0.97). – by Mark Leiser
Reference:
Poveda A, et al. Abstract 6002. Scheduled for presentation at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
Disclosures:
AstraZeneca and Merck Sharp & Dohme funded this study. Poveda reports consultant/advisory roles with AstraZeneca, Clovis Oncology, PharmaMar, Roche and Tesaro, as well as travel, accommodations or expenses from PharmaMar. Please see the abstract for all other researchers’ relevant financial disclosures.
Perspective
Back to TopKonstantin Zakashansky, MD, FACOG
The SOLO-2 study and Study 19 established the efficacy of olaparib maintenance therapy for women with platinum-sensitive, relapsed ovarian cancer with a germline BRCA mutation.
Prior results from SOLO-2 demonstrated that women treated with olaparib had investigator-assessed median PFS of 19.1 months, compared with 5.5 months for women who received placebo. At the time of the initial presentation, however, questions were raised regarding clinical uncertainty of the benefit associated with olaparib maintenance — primarily whether the PFS benefit observed with olaparib tablets in the trial would translate to a long-term OS benefit.
These data answer that question. As the researchers stated, maintenance olaparib provided “an unprecedented improvement” in median OS compared with placebo in this subgroup of women with ovarian cancer. This is the largest improvement in OS reported to date from a trial of women with recurrent ovarian cancer.
PARP inhibitor trials have revolutionized therapy for ovarian cancer in the front-line and recurrent settings. All of the recently presented trials show significant improvements in PFS. OS, however, is considered the most clinically relevant endpoint in oncology trials and remains the gold standard. SOLO-2 provides those data, showing significant improvement in OS and validating earlier reported PFS benefits associated with PARP inhibition.
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Poveda A, et al. Abstract 6002. Scheduled for presentation at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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