Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer.

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. (Funded by ARCAGY Research and others; PAOLA-1 ClinicalTrials.gov number, NCT02477644.).

• Authors: Isabelle Ray-Coquard, Patricia Pautier, Sandro Pignata, David Pérol, Antonio González-Martín, Regina Berger, Keiichi Fujiwara, Ignace Vergote, Nicoletta Colombo, Johanna Mäenpää, Frédéric Selle, Jalid Sehouli, Domenica Lorusso, Eva M Guerra Alía, Alexander Reinthaller, Shoji Nagao, Claudia Lefeuvre-Plesse, Ulrich Canzler, Giovanni Scambia, Alain Lortholary, Frederik Marmé, Pierre Combe, Nikolaus de Gregorio, Manuel Rodrigues, Paul Buderath, Coraline Dubot, Alexander Burges, Benoît You, Eric Pujade-Lauraine, Philipp Harter, PAOLA-1 Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 381 Issue 25 Pg. 2416-2428 (12 19 2019) ISSN: 1533-4406 [Electronic] United States
• PMID: 31851799 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Massachusetts Medical Society.

Chemical References

• Phthalazines
• Piperazines
• Poly(ADP-ribose) Polymerase Inhibitors
• Bevacizumab
• olaparib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bevacizumab (administration & dosage, adverse effects)
• Combined Modality Therapy
• Double-Blind Method
• Female
• Humans
• Maintenance Chemotherapy
• Middle Aged
• Ovarian Neoplasms (drug therapy, mortality, surgery)
• Phthalazines (administration & dosage, adverse effects)
• Piperazines (administration & dosage, adverse effects)
• Poly(ADP-ribose) Polymerase Inhibitors (adverse effects, therapeutic use)
• Progression-Free Survival
• Quality of Life