Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Schouten, PC; Schmidt, S; Becker, K; Thiele, H; Nürnberg, P; Richters, L; Ernst, C; Treilleux, I; Medioni, J; Heitz, F; Pisano, C; Garcia, Y; Petru, E; Hietanen, S; Colombo, N; Vergote, I; Nagao, S; Linn, SC; Pujade-Lauraine, E; Ray-Coquard, I; Harter, P; Hahnen, E; Schmutzler, RK.
Olaparib Addition to Maintenance Bevacizumab Therapy in Ovarian Carcinoma With BRCA-Like Genomic Aberrations.
JAMA Netw Open. 2024; 7(4):e245552 Doi: 10.1001/jamanetworkopen.2024.5552 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Petru Edgar
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: 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.
Find related publications in this database (using NLM MeSH Indexing): Pregnancy - administration & dosage; Humans - administration & dosage; Female - administration & dosage; Adult - administration & dosage; Middle Aged - administration & dosage; Aged - administration & dosage; Aged, 80 and over - administration & dosage; Carcinoma, Ovarian Epithelial - drug therapy, genetics; Bevacizumab - therapeutic use; BRCA1 Protein - genetics; Cohort Studies - administration & dosage; BRCA2 Protein - genetics; Ovarian Neoplasms - drug therapy, genetics; Carcinoma - administration & dosage; Genomics - administration & dosage; Biomarkers - administration & dosage; Phthalazines - administration & dosage; Piperazines - administration & dosage