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Adding the PARP inhibitor olaparib to bevacizumab after first-line chemotherapy for advanced ovarian cancer roughly doubled the time without progression in women whose tumours had defective DNA repair, but did nothing for those without it.
Double-blind, placebo-controlled phase 3 trial of 806 patients with newly diagnosed advanced high-grade ovarian cancer who had responded to platinum-taxane chemotherapy with bevacizumab, randomised 2:1 to two years of olaparib or placebo added to bevacizumab maintenance. Primary endpoint was investigator-assessed PFS.
Median PFS was 22.1 vs 16.6 months overall (HR 0.59), but 37.2 vs 17.7 months (HR 0.33) in homologous-recombination-deficient (HRD) tumours and no different in HRD-negative tumours (HR 1.00). The 2023 OS analysis showed a survival benefit in HRD-positive disease (5-year OS 65.5% vs 48.4%, HR 0.62). It established HRD testing as a decision tool and olaparib plus bevacizumab as a first-line maintenance standard for HRD-positive ovarian cancer.
Women with newly diagnosed advanced ovarian cancer should have their tumour tested for BRCA mutations and homologous recombination deficiency, because those who are HRD-positive gain years of additional disease control and better survival from adding olaparib to bevacizumab maintenance. Those who are HRD-negative gain nothing from olaparib in this combination and should not be exposed to its toxicity and cost. HRD testing has become a routine part of ovarian cancer care as a result.
Shares Giovanni Scambia, Synthetic lethality, High-grade serous ovarian cancer, Platinum-sensitive ovarian cancer.
Shares Isabelle Ray-Coquard, High-grade serous ovarian cancer, Platinum-sensitive ovarian cancer, Homologous recombination deficiency (HRD).
Shares HRD & BRCA testing, Homologous recombination deficiency (HRD), PARP, PARP inhibitors.
Shares High-grade serous ovarian cancer, Platinum-sensitive ovarian cancer, PARP, PARP inhibitors.
Shares Synthetic lethality, Synthetic lethality approaches, Germline vs somatic mutations, PARP.
Shares Platinum-sensitive ovarian cancer, PARP inhibitors, Olaparib, Merck & Co. (MSD).
Shares Platinum-sensitive ovarian cancer, Homologous recombination deficiency (HRD), PARP, VEGF / VEGFR.
Shares HRD & BRCA testing, High-grade serous ovarian cancer, Homologous recombination deficiency (HRD), PARP.