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- Title
Olaparib Addition to Maintenance Bevacizumab Therapy in Ovarian Carcinoma With BRCA-Like Genomic Aberrations.
- Authors
Schouten, Philip C.; Schmidt, Sandra; Becker, Kerstin; Thiele, Holger; Nürnberg, Peter; Richters, Lisa; Ernst, Corinna; Treilleux, Isabelle; Medioni, Jacques; Heitz, Florian; Pisano, Carmela; Garcia, Yolanda; Petru, Edgar; Hietanen, Sakari; Colombo, Nicoletta; Vergote, Ignace; Nagao, Shoji; Linn, Sabine C.; Pujade-Lauraine, Eric; Ray-Coquard, Isabelle
- Abstract
Key Points: Question: Is olaparib maintenance treatment associated with longer survival in patients with ovarian cancer tumors with and without a previously established BRCA-like genomic profile? Findings: This cohort study was a secondary biomarker-by-treatment interaction analysis of 469 patients from a randomized clinical trial comparing the bevacizumab plus olaparib and bevacizumab plus placebo groups. Patients with BRCA-like tumors had a longer progression-free survival after olaparib vs placebo, but there was no significant difference in patients with a non–BRCA-like tumor after olaparib vs placebo. Meaning: The findings of this study suggest that the BRCA-like classifier can be used as a biomarker for olaparib maintenance therapy. Importance: Testing for homologous recombination deficiency is required for the optimal treatment of high-grade epithelial ovarian cancer. The search for accurate biomarkers is ongoing. Objective: To investigate whether progression-free survival (PFS) and overall survival (OS) of patients with high-grade epithelial ovarian cancer treated with maintenance olaparib or placebo differed between patients with a tumor BRCA-like genomic profile and patients without a tumor BRCA-like profile. Design, Setting, and Participants: This cohort study was a secondary analysis of the PAOLA-1 randomized clinical trial that compared olaparib plus bevacizumab with placebo plus bevacizumab as maintenance treatment in patients with advanced high-grade ovarian cancer after a good response to first-line platinum with taxane chemotherapy plus bevacizumab, irrespective of germline or tumor BRCA1/2 mutation status. All patients with available tumor DNA were included in the analysis. The current analysis tested for an interaction between BRCA-like status and olaparib treatment on survival outcomes. The original trial was conducted between July 2015 and September 2017; at the time of data extraction for analysis in March 2022, a median follow-up of 54.1 months (IQR, 28.5-62.2 months) and a total follow-up time of 21 711 months was available, with 336 PFS and 245 OS events. Exposures: Tumor homologous recombination deficiency was assessed using the BRCA-like copy number aberration profile classifier. Myriad MyChoice CDx was previously measured. The trial was randomized between the olaparib and bevacizumab and placebo plus bevacizumab groups. Main Outcomes and Measures: This secondary analysis assessed hazard ratios (HRs) of olaparib vs placebo among biomarker strata and tested for interaction between BRCA-like status and olaparib treatment on PFS and OS, using Cox proportional hazards regression. Results: A total of 469 patients (median age, 60 [range 26-80] years) were included in this study. The patient cohort consisted of women with International Federation of Gynaecology and Obstetrics stage III (76%) high-grade serous (95%) ovarian cancer who had no evaluable disease or complete remission at initial or interval debulking surgery (76%). Thirty-one percent of the tumor samples (n = 138) harbored a pathogenic BRCA mutation, and BRCA-like classification was performed for 442 patients. Patients with a BRCA-like tumor had a longer PFS after olaparib treatment than after placebo (36.4 vs 18.6 months; HR, 0.49; 95% CI, 0.37-0.65; P <.001). No association of olaparib with PFS was found in patients with a non–BRCA-like tumor (17.6 vs 16.6 months; HR, 1.02; 95% CI, 0.68-1.51; P =.93). The interaction was significant (P =.004), and HRs and P values (for interaction) were similar in the relevant subgroups, OS, and multivariable analyses. Conclusions and Relevance: In this secondary analysis of the PAOLA-1 randomized clinical trial, patients with a BRCA-like tumor, but not those with a non–BRCA-like tumor, had a significantly longer survival after olaparib plus bevacizumab treatment than placebo plus bevacizumab treatment. Thus, the BRCA1-like classifier could be used as a biomarker for olaparib plus bevacizumab as a maintenance treatment. This cohort study examines overall and progression-free survival, using a BRCA-like genomic copy number aberration profile classifier, in patients with ovarian cancer receiving olaparib plus bevacizumab or placebo plus bevacizumab.
- Subjects
THERAPEUTIC use of antineoplastic agents; BRCA genes; SECONDARY analysis; RESEARCH funding; FISHER exact test; CHROMOSOME abnormalities; DNA; DESCRIPTIVE statistics; MULTIVARIATE analysis; CHI-squared test; MANN Whitney U Test; LONGITUDINAL method; CANCER chemotherapy; KAPLAN-Meier estimator; LOG-rank test; RESEARCH; OVARIAN epithelial cancer; PROGRESSION-free survival; GENETIC mutation; CONFIDENCE intervals; OVERALL survival; PROPORTIONAL hazards models; REGRESSION analysis; EVALUATION
- Publication
JAMA Network Open, 2024, Vol 7, Issue 4, pe245552
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2024.5552