As Maintenance Therapy, Olaparib's Benefits Continue

The PARP inhibitor olaparib was approved in 2018 by the FDA as a first-line maintenance therapy for women with advanced BRCA-mutated ovarian cancer following completion of platinum-based chemotherapy. The decision was based on the randomized phase III SOLO1 trial, which found that the risk of disease progression or death was 70% lower with olaparib than with placebo after a median of 41 months (N Engl J Med 2018;379:2495–505).

Now, a 5-year analysis of the data shows that patients treated with olaparib for 2 years had a median progression-free survival (PFS) 3.5 years longer (56 months versus 13.8 months) than those who received placebo (Lancet Oncol 2021 Oct 26 [Epub ahead of print]). The most common grade 3 and 4 adverse events among the 260 patients in the olaparib arm were anemia (22%) and neutropenia (8%). Serious adverse events—but no deaths—occurred in 21% of the olaparib group and 13% of the placebo group.

“The [initial] results of the SOLO1 study set a new standard of care for women with BRCA-mutated newly diagnosed advanced ovarian cancer,” says Susana Banerjee, PhD, of The Royal Marsden National Health Service Foundation Trust and The Institute of Cancer Research in London, UK. Nonetheless, “it is important to check that effectiveness is maintained over time with longer patient follow-up. We have [now] shown that the effectiveness is maintained beyond the point at which treatment was stopped, which is an important point.

“This 5-year follow-up shows the long-term benefit of 2 years of maintenance olaparib, and that there was no increase in toxicities,” Banerjee continues, adding that no new toxicities emerged since the initial report. Importantly, PFS was extended regardless of whether patients were considered high- or low-risk, or which BRCA mutation they carried.

Banerjee and her fellow researchers note that quality of life during maintenance therapy was not impaired. Instead, patients who received olaparib had more time without “symptoms of toxicity” than those in the placebo group. The researchers also found that PFS was 13.6 months longer when patients began maintenance therapy immediately after completing chemotherapy than when it began only upon relapse.

“These findings have demonstrated benefit to patients beyond what has previously been seen by any other therapy options. They are dramatically changing the landscape for newly diagnosed ovarian cancer, potentially being able to cure more patients of their ovarian cancer than ever before,” says Ashley Haggerty, MD, of the Hospital of the University of Pennsylvania in Philadelphia, who wasn't involved in the research.

Results of the phase III PAOLA-1 trial were consistent with SOLO1. PAOLA-1 investigators compared olaparib with placebo as a maintenance therapy in patients—with and without BRCA mutations—who received chemotherapy plus the antiangiogenic agent bevacizumab followed by bevacizumab alone (N Engl J Med 2019;381:2416-28). Patients in all subgroups did better when they received olaparib; those with homologous recombination deficient-positive tumors fared particularly well, with a median PFS of 37.2 months vs. 17.7 months, respectively.

These findings suggest that PARP inhibitors are effective not just for those with BRCA mutations, but potentially for all patients. If so, long-term remission, or even a cure, may be possible, researchers say. “Discussion of the use of PARP inhibitors should be standard of care for all newly diagnosed ovarian cancer patients,” Haggerty says. –Gail Dutton

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