Olaparib maintenance therapy extends progression-free survival in women with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation, according to results from the SOLO2/ENGOT-Ov21 trial.
Olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, is approved in the European Union and other countries as maintenance treatment for women with platinum-sensitive, relapsed ovarian cancer and a germline BRCA1/2 mutation - and in the US as monotherapy for advanced ovarian cancer patients with a germline BRCA1/2 mutation.
Dr. Eric Pujade-Lauraine, from France’s Universite Paris Descartes, and colleagues from 16 countries evaluated olaparib maintenance treatment in a randomized, placebo-controlled, phase 3 trial of 295 women with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation.
AstraZeneca, the drug’s manufacturer, funded the study.
At data cutoff, 43% of the 196 women assigned to olaparib and 13% of the 99 assigned to placebo were still receiving treatment, according to the July 25 Lancet Oncology online report.
After a median follow-up of about 22 months, median progression-free survival was significantly longer among olaparib recipients than placebo recipients (19.1 vs. 5.5 months). Kaplan-Meier estimated progression-free survival was 65% at 12 months and 43% at 24 months with olaparib, compared with 21% and 15%, respectively, with placebo.
Findings were consistent regardless of whether women had received prior bevacizumab therapy and whether they had confirmed/suspected deleterious BRCA1/2 mutations.
Self-reported quality-of-life measures did not differ appreciably between olaparib and placebo recipients.
The most common adverse events in both groups were nausea, fatigue or asthenia, vomiting, abdominal pain, and diarrhea. The incidence of anemia was higher among olaparib than placebo recipients (18% vs. 1% required blood transfusions), as were rates of dose interruption, dose reduction, and drug discontinuation due to adverse events.
Seventy-two participants died during the study, including 45 (23%) in the olaparib group and 27 (27%) in the placebo group.
“Our results confirm that olaparib can achieve a significant prolongation of progression-free survival in this patient population with no appreciable detrimental effect observed for patients’ quality of life,” the researchers conclude. “The favorable safety profile in SOLO2 enabled most patients receiving olaparib to maintain full dosing throughout their maintenance treatment.”
“Previous trials of extended maintenance with conventional chemotherapy in ovarian cancer have not shown benefit,” write Dr. Michael A. Bookman from US Oncology Research, Tucson, Arizona, and Dr. Henry C. Kitchener from University of Manchester, UK, in a related editorial. “By contrast, bevacizumab maintenance following concurrent use with chemotherapy has contributed to a modest gain in progression-free survival, without improvement in overall survival for those with ovarian cancer. Hence, more mature data from the SOLO2 trial and other maintenance trials are crucial.”
“Treatment with PARP inhibitors is not generally curative, and extended use will result in many patients developing resistance through clonal BRCA1/2 revertant mutations and other pathways, which could be persistent, thereby reducing the effectiveness of subsequent interventions,” they note. “A better understanding of the optimal sequence and duration of therapy in women with small volume asymptomatic residual disease could enhance the overall benefit of PARP inhibitors as part of an integrated approach to disease management.”
Dr. Gonzalo Giornelli from Instituto Alexander Fleming, Buenos Aires, Argentina, who recently reviewed the management of relapsed ovarian cancer, told Reuters Health by email, "Ovarian cancer relapses in more than three quarters of patients, mostly because the same amount of patients are diagnosed with advanced disease. Knowing the BRCA status of a patient as early as possible would allow us to consider this maintenance therapy after platinum-sensitive relapse, which will occur mostly in the first 2 years after diagnosis.”
“In a patient who relapses (as 70% do), we know she will progress,” he explained. “To prolong the time she is out of chemotherapy is a valuable goal in the management of these patients.”
Dr. Pujade-Lauraine did not respond to a request for comment.
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