Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer.
(2019) The New England journal of medicine — Vol. 381, n° 25, p. 2416-2428 (2019)
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- Abstract
- Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of mutation status is unknown. We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a mutation. (Funded by ARCAGY Research and others; PAOLA-1 ClinicalTrials.gov number, NCT02477644.).
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Ray-Coquard, I., Pautier, P., Pignata, S., Pérol, D., González-Martín, A., Berger, R., Fujiwara, K., Vergote, I., Colombo, N., Mäenpää, J., Selle, F., Sehouli, J., Lorusso, D., Guerra Alía, E. M., Reinthaller, A., Nagao, S., Lefeuvre-Plesse, C., Canzler, U., Scambia, G., et al. (2019). Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. The New England journal of medicine, 381(25), 2416-2428. https://doi.org/10.1056/NEJMoa1911361 (Original work published 2019)