Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer

Ray-Coquard, I.; Pautier, P.; Pignata, S.; Perol, D.; Gonzalez-Martin, A.; Berger, R.; Fujiwara, K.; Vergote, I.; Colombo, N.; Maenpaa, J.; Selle, F.; Sehouli, J.; Lorusso, D.; Alia, E. M. Guerra; Reinthaller, A.; Nagao, S.; Lefeuvre-Plesse, C.; Canzler, U.; Scambia, G.; Lortholary, A.; Marme, F.; Combe, P.; de Gregorio, N.; Rodrigues, M.; Buderath, P.; Dubot, C.; Burges, A.; You, B.; Pujade-Lauraine, E. und Harter, P. (2019): Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. In: New England Journal of Medicine, Bd. 381, Nr. 25: S. 2416-2428

Abstract

BACKGROUND Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS 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 BRCA 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. RESULTS 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 BRCA 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 BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. CONCLUSIONS 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 BRCA mutation.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0028-4793
• Sprache: Englisch