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In women with newly diagnosed advanced BRCA-mutated ovarian cancer who had responded to chemotherapy, two years of the PARP inhibitor olaparib kept far more of them free of progression than placebo, and the effect persisted for years after the tablets stopped. It moved PARP inhibitors into first-line maintenance and made BRCA testing at diagnosis routine.
Double-blind, placebo-controlled phase 3 trial of 391 patients with newly diagnosed advanced high-grade ovarian cancer and a BRCA1/2 mutation who had responded to platinum-based chemotherapy, randomised 2:1 to two years of olaparib or placebo maintenance. Primary endpoint was investigator-assessed PFS.
PFS HR was 0.30, with 3-year PFS 60% vs 27%. Long-term follow-up showed a durable effect after treatment stopped: 7-year OS 67% vs 46.5% (HR 0.55) and about 45% of olaparib patients progression-free at seven years, suggesting a fraction were cured. It moved PARP inhibitors from recurrent disease to first-line maintenance and made BRCA testing at diagnosis mandatory.
Every woman diagnosed with advanced high-grade ovarian cancer should be tested for BRCA mutations at diagnosis, because those who carry one should receive two years of olaparib after chemotherapy, which greatly extends the time in remission and improves long-term survival. The plateau in the survival curves suggests some patients are cured by this approach. Toxicity is mostly anaemia, fatigue and nausea, and the two-year limit appears sufficient.
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