TY - JOUR
T1 - Maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian cancer
T2 - Main analysis of second progression-free survival in the phase III PAOLA-1/ENGOT-ov25 trial
AU - González-Martín, Antonio
AU - Desauw, Christophe
AU - Heitz, Florian
AU - Cropet, Claire
AU - Gargiulo, Piera
AU - Berger, Regina
AU - Ochi, Hiroyuki
AU - Vergote, Ignace
AU - Colombo, Nicoletta
AU - Mirza, Mansoor R
AU - Tazi, Youssef
AU - Canzler, Ulrich
AU - Zamagni, Claudio
AU - Guerra-Alia, Eva M
AU - Levaché, Charles B
AU - Marmé, Frederik
AU - Bazan, Fernando
AU - de Gregorio, Nikolaus
AU - Dohollou, Nadine
AU - Fasching, Peter A
AU - Scambia, Giovanni
AU - Rubio-Pérez, María J
AU - Milenkova, Tsveta
AU - Costan, Cristina
AU - Pautier, Patricia
AU - Ray-Coquard, Isabelle
AU - PAOLA1/ENGOT-ov25 investigators
N1 - Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.
PY - 2022
Y1 - 2022
N2 - BACKGROUND: PAOLA-1/ENGOT-ov25 (NCT02477644) demonstrated a significant progression-free survival (PFS) benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in newly diagnosed, advanced ovarian cancer. We report the prespecified main second progression-free survival (PFS2) analysis for PAOLA-1.METHODS: This randomised, double-blind, phase III trial was conducted in 11 countries. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were in response after first-line platinum-based chemotherapy plus bevacizumab. Patients were randomised 2:1 to olaparib (300 mg twice daily) or placebo for up to 24 months; all patients received bevacizumab (15 mg/kg every 3 weeks) for up to 15 months. Primary PFS end-point was reported previously. Time from randomisation to second disease progression or death was a key secondary end-point included in the hierarchical-testing procedure.RESULTS: After a median follow-up of 35.5 months and 36.5 months, respectively, median PFS2 was 36.5 months (olaparib plus bevacizumab) and 32.6 months (placebo plus bevacizumab), hazard ratio 0.78; 95% confidence interval (CI) 0.64-0.95; P = 0.0125. Median time to second subsequent therapy or death was 38.2 months (olaparib plus bevacizumab) and 31.5 months (placebo plus bevacizumab), hazard ratio 0.78; 95% CI 0.64-0.95; P = 0.0115. Seventy-two (27%) patients in the placebo plus bevacizumab group received a poly(ADP-ribose) polymerase inhibitor as first subsequent therapy. No new safety signals were observed for olaparib plus bevacizumab.CONCLUSION: In newly diagnosed, advanced ovarian cancer, maintenance olaparib plus bevacizumab provided continued benefit beyond first progression, with a significant PFS2 improvement and a time to second subsequent therapy or death delay versus placebo plus bevacizumab.
AB - BACKGROUND: PAOLA-1/ENGOT-ov25 (NCT02477644) demonstrated a significant progression-free survival (PFS) benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in newly diagnosed, advanced ovarian cancer. We report the prespecified main second progression-free survival (PFS2) analysis for PAOLA-1.METHODS: This randomised, double-blind, phase III trial was conducted in 11 countries. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were in response after first-line platinum-based chemotherapy plus bevacizumab. Patients were randomised 2:1 to olaparib (300 mg twice daily) or placebo for up to 24 months; all patients received bevacizumab (15 mg/kg every 3 weeks) for up to 15 months. Primary PFS end-point was reported previously. Time from randomisation to second disease progression or death was a key secondary end-point included in the hierarchical-testing procedure.RESULTS: After a median follow-up of 35.5 months and 36.5 months, respectively, median PFS2 was 36.5 months (olaparib plus bevacizumab) and 32.6 months (placebo plus bevacizumab), hazard ratio 0.78; 95% confidence interval (CI) 0.64-0.95; P = 0.0125. Median time to second subsequent therapy or death was 38.2 months (olaparib plus bevacizumab) and 31.5 months (placebo plus bevacizumab), hazard ratio 0.78; 95% CI 0.64-0.95; P = 0.0115. Seventy-two (27%) patients in the placebo plus bevacizumab group received a poly(ADP-ribose) polymerase inhibitor as first subsequent therapy. No new safety signals were observed for olaparib plus bevacizumab.CONCLUSION: In newly diagnosed, advanced ovarian cancer, maintenance olaparib plus bevacizumab provided continued benefit beyond first progression, with a significant PFS2 improvement and a time to second subsequent therapy or death delay versus placebo plus bevacizumab.
UR - http://www.scopus.com/inward/record.url?scp=85137304144&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2022.07.022
DO - 10.1016/j.ejca.2022.07.022
M3 - Journal article
C2 - 36067615
SN - 0959-8049
VL - 174
SP - 221
EP - 231
JO - European journal of cancer (Oxford, England : 1990)
JF - European journal of cancer (Oxford, England : 1990)
ER -