Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer

Giovanni Scambia, I. Ray-Coquard, P. Pautier, S. Pignata, D. Pérol, A. González-Martín, R. Berger, K. Fujiwara, I. Vergote, N. Colombo, J. Mäenpää, F. Selle, J. Sehouli, D. Lorusso, E. M. Guerra Alía, A. Reinthaller, S. Nagao, C. Lefeuvre-Plesse, U. Canzler, A. LortholaryF. Marmé, P. Combe, N. De Gregorio, M. Rodrigues, P. Buderath, C. Dubot, A. Burges, B. You, E. Pujade-Lauraine, P. Harter

Risultato della ricerca: Contributo in rivistaArticolo in rivista

215 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)2416-2428
Numero di pagine13
RivistaNew England Journal of Medicine
Volume381
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Bevacizumab
  • Combined Modality Therapy
  • Double-Blind Method
  • Female
  • Humans
  • Maintenance Chemotherapy
  • Middle Aged
  • Ovarian Neoplasms
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Progression-Free Survival
  • Quality of Life

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