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

被引：2

作者：

Piha-Paul, Sarina A. ^{[1
]}

Tseng, Chieh ^{[1
]}

Leung, Cheuk Hong ^{[2
]}

Yuan, Ying ^{[2
]}

Karp, Daniel D. ^{[1
]}

Subbiah, Vivek ^{[1
]}

Hong, David ^{[1
]}

Fu, Siqing ^{[1
]}

Naing, Aung ^{[1
]}

Rodon, Jordi ^{[1
]}

Javle, Milind ^{[3
]}

Ajani, Jaffer A. ^{[3
]}

Raghav, Kanwal P. ^{[3
]}

Somaiah, Neeta ^{[4
]}

Mills, Gordon B. ^{[5
]}

Tsimberidou, Apostolia M. ^{[1
]}

Zheng, Xiaofeng ^{[7
]}

Chen, Ken ^{[7
]}

Meric-Bernstam, Funda ^{[1
,6
,8
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Phase Clin Trials Program 1, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX USA

[5] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Breast Surg Oncol, Houston, TX USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX USA

[8] Univ Texas MD Anderson Canc Ctr, Sheikh Khalifa Bin Zayed Nahyan Inst Personalized, Houston, TX USA

来源：

NPJ PRECISION ONCOLOGY | 2024年 / 8卷 / 01期

关键词：

HOMOLOGOUS RECOMBINATION REPAIR; BREAST-CANCER; PARP INHIBITOR; POLY(ADP-RIBOSE) POLYMERASE; GENOMIC INSTABILITY; OLAPARIB; MUTATIONS; COMBINATION; CELLS; SUSCEPTIBILITY;

D O I：

10.1038/s41698-024-00634-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：14

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