Phase II Study of Talazoparib in Advanced Cancers With BRCA1/2, DNA Repair, and PTEN Alterations

Authors

Sarina A Piha-Paul
Chieh Tseng
Cheuk Hong Leung
Ying Yuan
Daniel D Karp
Vivek Subbiah
David Hong
Siqing Fu
Aung Naing
Jordi Rodon
Milind Javle
Jaffer A Ajani
Kanwal P Raghav
Neeta Somaiah
Gordon B Mills
Apostolia M Tsimberidou
Xiaofeng Zheng
Ken Chen
Funda Meric-Bernstam

Publication Date

7-31-2024

Journal

NPJ Precision Oncology

Abstract

Cancer cells with BRCA1/2 deficiencies are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We evaluated the efficacy of talazoparib in DNA-Damage Repair (DDR)-altered patients. In this phase II trial, patients were enrolled onto one of four cohorts based on molecular alterations: (1) somatic BRCA1/2, (2) other homologous recombination repair pathway, (3) PTEN and (4) germline BRCA1/2. The primary endpoint was a clinical benefit rate (CBR): complete response, partial response or stable disease ≥24 weeks. 79 patients with a median of 4 lines of therapy were enrolled. CBR for cohorts 1-4 were: 32.5%, 19.7%, 9.4% and 30.6%, respectively. PTEN mutations correlated with reduced survival and a trend towards shorter time to progression.Talazoparib demonstrated clinical benefit in selected DDR-altered patients. PTEN mutations/loss patients derived limited clinical benefit. Further study is needed to determine whether PTEN is prognostic or predictive of response to PARP inhibitors.

Keywords

Targeted therapies, Targeted therapies

Comments

Supplementary Material

Data Availability Statement

PMID: 39085400

DOI

10.1038/s41698-024-00634-6

PMID

39085400

PMCID

PMC11291882

PubMedCentral® Posted Date

July 2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes