Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer

TY - JOUR

T1 - Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer

AU - Ray-Coquard, Isabelle

AU - Pautier, Patricia

AU - Pignata, Sandro

AU - Pérol, David

AU - González-Martín, Antonio

AU - Berger, Regina

AU - Fujiwara, Keiichi

AU - Vergote, Ignace

AU - Colombo, Nicoletta

AU - Mäenpää, Johanna

AU - Selle, Frédéric

AU - Sehouli, Jalid

AU - Lorusso, Domenica

AU - Guerra Alía, Eva M

AU - Reinthaller, Alexander

AU - Nagao, Shoji

AU - Lefeuvre-Plesse, Claudia

AU - Canzler, Ulrich

AU - Scambia, Giovanni

AU - Lortholary, Alain

AU - Marmé, Frederik

AU - Combe, Pierre

AU - de Gregorio, Nikolaus

AU - Rodrigues, Manuel

AU - Buderath, Paul

AU - Dubot, Coraline

AU - Burges, Alexander

AU - You, Benoît

AU - Pujade-Lauraine, Eric

AU - Harter, Philipp

AU - PAOLA-1 Investigators

N1 - Copyright © 2019 Massachusetts Medical Society.

PY - 2019/12/19

Y1 - 2019/12/19

N2 - 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.).

AB - 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.).

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Bevacizumab/administration & dosage

KW - Combined Modality Therapy

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Maintenance Chemotherapy

KW - Middle Aged

KW - Ovarian Neoplasms/drug therapy

KW - Phthalazines/administration & dosage

KW - Piperazines/administration & dosage

KW - Poly(ADP-ribose) Polymerase Inhibitors/adverse effects

KW - Progression-Free Survival

KW - Quality of Life

U2 - 10.1056/NEJMoa1911361

DO - 10.1056/NEJMoa1911361

M3 - SCORING: Journal article

C2 - 31851799

VL - 381

SP - 2416

EP - 2428

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 25

ER -