Reference Detail

Ref Type

Abstract

PMID

Authors

S.R. Joris H. Denys J.J. Collignon M. Rasschaert D. T'Kint de Roodenbeke F.P. Duhoux J-L. Canon S. Tejpar J. Mebis L. Decoster P.G. Aftimos J. De Grève

Title

52P Efficacy of olaparib in advanced cancers with germline or somatic tumor mutations in BRCA1, BRCA2, CHEK2 and ATM: A Belgian precision tumor-agnostic phase II study

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	34	Suppl_2	October 2023

URL

https://www.annalsofoncology.org/article/S0923-7534(23)03713-4/fulltext

Abstract Text

The Belgian Precision initiative aims to maximize the implementation of tumor-agnostic NGS in patients with advanced cancer and enhance access to molecularly-guided treatment options (MGTOs). Academic tumor-agnostic basket phase 2 studies are part of this initiative. The current investigator-driven trial aimed to investigate olaparib efficacy in advanced cancers with a pathogenic or likely pathogenic mutation (germline or somatic) in a gene that plays a role in homologous recombination (HR). Methods Open-label multi-cohort phase 2 study that examines the efficacy of olaparib in patients with an HR gene mutation in their tumor and failed SoC. 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 (type I error rate of 5% and a power of 80% when the true response rate is 20%). 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 (N=27) and 21% in the BRCA2 (N=27) mutated 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 CR with 19+ months on treatment. mPFS in responding patients is 14+ months (5-34+ months). The clinical benefit rate was 63% in the BRCA1 and 46% in the BRCA2 mutated cohorts. No clinical activity was observed in the ATM (N=13) and CHEK2 (N=14) cohorts. Safety data were consistent with the known profile of olaparib. Conclusions 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 with real-world documentation of efficacy in a retrospective register.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CHEK2 mutant	Advanced Solid Tumor	no benefit	Olaparib	Phase II	Actionable	In a Phase II trial, Lynparza (olaparib) treatment did not demonstrate clinical activity in patients with advanced solid tumors harboring ATM (n=13) or CHEK2 (n=14) mutations (Ann Oncol (2023) 34 (suppl_2): S242; NCT03967938).	detail...
ATM mutant	Advanced Solid Tumor	conflicting	Olaparib	Phase II	Actionable	In a Phase II trial, Lynparza (olaparib) treatment did not demonstrate clinical activity in patients with advanced solid tumors harboring ATM (n=13) or CHEK2 (n=14) mutations (Ann Oncol (2023) 34 (suppl_2): S242; NCT03967938).	detail...