TY - JOUR
T1 - Efficacy of maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed, advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial
AU - Harter, Philipp
AU - Mouret-Reynier, Marie Ange
AU - Pignata, Sandro
AU - Cropet, Claire
AU - González-Martín, Antonio
AU - Bogner, Gerhard
AU - Fujiwara, Keiichi
AU - Vergote, Ignace
AU - Colombo, Nicoletta
AU - Nøttrup, Trine Jakobi
AU - Floquet, Anne
AU - El-Balat, Ahmed
AU - Scambia, Giovanni
AU - Guerra Alia, Eva Maria
AU - Fabbro, Michel
AU - Schmalfeldt, Barbara
AU - Hardy-Bessard, Anne-Claire
AU - Runnebaum, Ingo
AU - Pujade-Lauraine, Eric
AU - Ray-Coquard, Isabelle
PY - 2022
Y1 - 2022
N2 - Objectives. Adding maintenance olaparib to bevacizumab provided a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the randomized, double-blind PAOLA-1/ENGOT-ov25 trial (NCT02477644). We analyzed PFS by clinical risk and biomarker status. Methods. Patients received olaparib 300 mg twice daily for up to 24 months plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total, or placebo plus bevacizumab. This post hoc exploratory analysis evaluated PFS in patients classified as higher risk (stage III with upfront surgery and residual disease or neoadjuvant chemotherapy; stage IV) or lower risk (stage III with upfront surgery and no residual disease), and by biomarker status. Results. Of 806 randomized patients, 74% were higher risk and 26% were lower risk. After a median 22.9 months of follow-up, PFS favored olaparib plus bevacizumab versus placebo plus bevacizumab in higher risk patients (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.49-0.74) and lower-risk patients (0.46; 0.30-0.72). Olaparib plus bevacizumab provided a substantial PFS benefit versus bevacizumab alone in the homologous recombination deficiency (HRD)-positive subgroup (higher risk: HR 0.39; 95% CI 0.28-0.54 and lower risk: 0.15; 0.07-0.30), with 24-month PFS rates in lower-risk patients of 90% versus 43%, respectively (Kaplan-Meier estimates). Conclusions. In PAOLA-1, maintenance olaparib plus bevacizumab provided a substantial PFS benefit in HRDpositive patients with a reduction of risk of progression or death of 61% in the higher-risk group and of 85% in the lower-risk group compared with bevacizumab alone. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
AB - Objectives. Adding maintenance olaparib to bevacizumab provided a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the randomized, double-blind PAOLA-1/ENGOT-ov25 trial (NCT02477644). We analyzed PFS by clinical risk and biomarker status. Methods. Patients received olaparib 300 mg twice daily for up to 24 months plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total, or placebo plus bevacizumab. This post hoc exploratory analysis evaluated PFS in patients classified as higher risk (stage III with upfront surgery and residual disease or neoadjuvant chemotherapy; stage IV) or lower risk (stage III with upfront surgery and no residual disease), and by biomarker status. Results. Of 806 randomized patients, 74% were higher risk and 26% were lower risk. After a median 22.9 months of follow-up, PFS favored olaparib plus bevacizumab versus placebo plus bevacizumab in higher risk patients (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.49-0.74) and lower-risk patients (0.46; 0.30-0.72). Olaparib plus bevacizumab provided a substantial PFS benefit versus bevacizumab alone in the homologous recombination deficiency (HRD)-positive subgroup (higher risk: HR 0.39; 95% CI 0.28-0.54 and lower risk: 0.15; 0.07-0.30), with 24-month PFS rates in lower-risk patients of 90% versus 43%, respectively (Kaplan-Meier estimates). Conclusions. In PAOLA-1, maintenance olaparib plus bevacizumab provided a substantial PFS benefit in HRDpositive patients with a reduction of risk of progression or death of 61% in the higher-risk group and of 85% in the lower-risk group compared with bevacizumab alone. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
KW - (max 6): Olaparib
KW - Bevacizumab
KW - Clinical risk
KW - Newly diagnosed
KW - Ovarian cancer
KW - (max 6): Olaparib
KW - Bevacizumab
KW - Clinical risk
KW - Newly diagnosed
KW - Ovarian cancer
UR - http://hdl.handle.net/10807/232463
U2 - 10.1016/j.ygyno.2021.12.016
DO - 10.1016/j.ygyno.2021.12.016
M3 - Article
SN - 1095-6859
VL - 164
SP - 254
EP - 264
JO - Gynecologic Oncology
JF - Gynecologic Oncology
ER -