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Ref Type Journal Article
PMID (42105598)
Authors Joris S, Denys H, Collignon J, Rasschaert M, de Roodenbeke DT, Duhoux FP, Canon JL, Tejpar S, Mebis J, Decoster L, Aftimos P, De Grève J
Title Efficacy of olaparib in advanced cancers with somatic or germline mutations in BAP1, BARD1, BRIP1 and PALB2.
Journal Vol Issue Date Pages Journal Short Title
ESMO open 11 5 2026 May 08 107693 ESMO Open
URL
Abstract Text Olaparib is registered for use in ovarian, breast, pancreatic and prostate cancers with a BRCA1/2 mutation and/or mutations in other homologous recombination deficiency (HRD) genes. HRD gene mutations are also found in other cancer types, and these cancers may also benefit from olaparib therapy. We aimed to evaluate the efficacy of olaparib in advanced cancers harboring a (likely) pathogenic germline or somatic mutation in a gene involved in homologous recombination (HR).This investigator-initiated, open-label, basket phase II trial evaluates the efficacy of olaparib in patients with advanced tumors harboring HR gene mutations following progression on standard-of-care therapies. Cohorts were stratified based on the presence of either somatic or germline mutations in the same HR-related gene. Although results from the completed cohorts have been previously published, this report presents a case series focusing on cohorts with rare gene alterations.In patients who harbor a tumor mutation in ARID1A, ATR, ATRX, BLM, CDK12, CHEK1, DDR2, ERCC4, FANCE, GEN1, MRE11A, NBN, POLE, RAD21, RAD50, RAD51C, RAD51D, RAD52 and SLX4, no responses were observed. In the BAP1, BARD1, BRIP1 and PALB2 cohorts, objective responses were detected.Olaparib demonstrated meaningful clinical activity across different cancer types with somatic or germline mutations in BAP1, BARD1, BRIP1 and PALB2.

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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
BRIP1 S624* soft tissue sarcoma predicted - sensitive Olaparib Case Reports/Case Series Actionable In a Phase II trial, treatment with Lynparza (olaparib) resulted in a clinical benefit rate of 62.5% (5/8) in advanced solid tumor patients harboring BRIP1 mutations, including a complete response in a patient with soft tissue sarcoma harboring BRIP1 S624* (reported as c.1871C>A) (PMID: 42105598). 42105598
PALB2 L1142Yfs*21 breast carcinoma predicted - sensitive Olaparib Case Reports/Case Series Actionable In a Phase II trial, treatment with Lynparza (olaparib) resulted in an objective response rate of 25.0% (2/8) and clinical benefit rate of 50.0% in advanced solid tumor patients harboring PALB2 mutations, including a partial response in a patient with breast carcinoma harboring PALB2 L1142Yfs*21 (reported as c.3424del) (PMID: 42105598). 42105598
BRIP1 T997Rfs*61 pancreatic adenocarcinoma predicted - sensitive Olaparib Case Reports/Case Series Actionable In a Phase II trial, treatment with Lynparza (olaparib) resulted in a clinical benefit rate of 62.5% in advanced solid tumor patients harboring BRIP1 mutations, including a partial response in a patient with pancreatic adenocarcinoma harboring BRIP1 T997Rfs*61 (reported as c.2990_2993del) (PMID: 42105598). 42105598
PALB2 R238* breast carcinoma predicted - sensitive Olaparib Case Reports/Case Series Actionable In a Phase II trial, treatment with Lynparza (olaparib) resulted in an objective response rate of 25.0% (2/8) and clinical benefit rate of 50.0% in advanced solid tumor patients harboring PALB2 mutations, including a complete response in a patient with breast carcinoma harboring PALB2 R238* (reported as c.712A>T) (PMID: 42105598). 42105598