Phase II study of talazoparib in advanced cancers with BRCA1/2, DNA repair, and PTEN alterations-Reference-Cited by-同舟云学术

Phase II study of talazoparib in advanced cancers with BRCA1/2, DNA repair, and PTEN alterations

Published:2024-07-31 Issue:1 Volume:8 Page:
ISSN:2397-768X
Container-title:npj Precision Oncology
language:en
Short-container-title:npj Precis. Onc.

Author:

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

Abstract

AbstractCancer 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.

Publisher

Springer Science and Business Media LLC

Link

https://www.nature.com/articles/s41698-024-00634-6.pdf

Reference56 articles.

1. Birkelbach, M. et al. Detection of impaired homologous recombination repair in NSCLC cells and tissues. J. Thorac. Oncol. 8, 279–286 (2013).

2. Hennessy, B. T. et al. Somatic mutations in BRCA1 and BRCA2 could expand the number of patients that benefit from poly (ADP ribose) polymerase inhibitors in ovarian cancer. J. Clin. Oncol. 28, 3570–3576 (2010).

3. George, J. et al. Nonequivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations. Clin. Cancer Res. 19, 3474-3484 (2013).

4. Gorringe, K. L. et al. Copy number analysis identifies novel interactions between genomic loci in ovarian cancer. PLoS One 5, e11408 (2010).

5. Konishi, H. et al. Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cells. Proc. Natl. Acad. Sci. USA 108, 17773–17778 (2011).