Efficacy of olaparib in advanced cancers with germline or somatic mutations in BRCA1, BRCA2, CHEK2 and ATM, a Belgian Precision tumor-agnostic phase II study.
Efficacy of olaparib in advanced cancers with germline or somatic mutations in BRCA1, BRCA2, CHEK2 and ATM, a Belgian Precision tumor-agnostic phase II study.pdf
[en] [en] BACKGROUND: The Belgian Precision initiative aims to maximize the implementation of tumor-agnostic next-generation sequencing in patients with advanced cancer and enhance access to molecularly guided treatment options. Academic tumor-agnostic basket phase II studies are part of this initiative. The current investigator-driven trial aimed to investigate the efficacy of olaparib in advanced cancers with a (likely) pathogenic mutation (germline or somatic) in a gene that plays a role in homologous recombination (HR).
PATIENTS AND METHODS: This open-label, multi-cohort, phase II study examines the efficacy of olaparib in patients with an HR gene mutation in their tumor and disease progression on standard of care. Patients with a somatic or germline mutation in the same gene define a cohort. For each cohort, a Simon minimax two-stage design was used. If a response was observed in the first 13 patients, 14 additional patients were included. Here, we report the results on four completed cohorts: patients with a BRCA1, BRCA2, CHEK2 or ATM mutation.
RESULTS: The overall objective response rate across different tumor types was 11% in the BRCA1-mutated (n = 27) and 21% in the BRCA2-mutated (n = 27) cohorts. Partial responses were seen in pancreatic cancer, gallbladder cancer, endocrine carcinoma of the pancreas and parathyroid cancer. One patient with a BRCA2 germline-mutated colon cancer has an ongoing complete response with 19+ months on treatment. Median progression-free survival in responding patients was 14+ months (5-34+ months). The clinical benefit rate was 63% in the BRCA1-mutated and 46% in the BRCA2-mutated cohorts. No clinical activity was observed in the ATM (n = 13) and CHEK2 (n = 14) cohorts.
CONCLUSION: Olaparib showed efficacy in different cancer types harboring somatic or germline mutations in the BRCA1/2 genes but not in ATM and CHEK2. Patients with any cancer type harboring BRCA1/2 mutations should have access to olaparib.
Disciplines :
Oncology
Author, co-author :
Joris, S; Department of Medical Oncology, UZ Brussel, Brussels. Electronic address: Sofie.Joris@uzbrussel.be
Denys, H; Department of Medical Oncology, University Hospital Ghent, Ghent
Collignon, Joëlle ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Rasschaert, M; UZA, Antwerpen
T'Kint de Roodenbeke, D; Institut Jules Bordet-Université libre de Bruxelles, Brussels
Duhoux, F P; Cliniques universitaires Saint-Luc, Brussels
Canon, J-L; GHdC, Charlerloi
Tejpar, S; UZ Leuven, Leuven
Mebis, J; Jessa Ziekenhuizen, Hasselt
Decoster, L; Department of Medical Oncology, UZ Brussel, Brussels
Aftimos, P; Institut Jules Bordet-Université libre de Bruxelles, Brussels
De Grève, J; Department of Medical Oncology, UZ Brussel, Brussels, Department of Medical Genetics, UZ Brussel, Brussels, Belgium
Language :
English
Title :
Efficacy of olaparib in advanced cancers with germline or somatic mutations in BRCA1, BRCA2, CHEK2 and ATM, a Belgian Precision tumor-agnostic phase II study.
This work was supported by pharmaceutical companies AstraZeneca (global) and Merckx for medication supply and financial contributions. Financial support was provided by Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society (project ID: 1145) and the Stichting Tegen Kanker (no grant number).
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