BACKGROUNDOlaparib 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.METHODSWe 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.RESULTSOf 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.CONCLUSIONSIn 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.

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., 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., Harter, P., Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer, <<NEW ENGLAND JOURNAL OF MEDICINE>>, 2019; 381 (25): 2416-2428. [doi:10.1056/NEJMoa1911361] [http://hdl.handle.net/10807/170615]

Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer

Scambia, Giovanni;
2019

Abstract

BACKGROUNDOlaparib 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.METHODSWe 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.RESULTSOf 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.CONCLUSIONSIn 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.
2019
Inglese
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., 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., Harter, P., Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer, <<NEW ENGLAND JOURNAL OF MEDICINE>>, 2019; 381 (25): 2416-2428. [doi:10.1056/NEJMoa1911361] [http://hdl.handle.net/10807/170615]
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