TY - JOUR
T1 - Phase II study of talazoparib in advanced cancers with BRCA1/2, DNA repair, and PTEN alterations
AU - Piha-Paul, Sarina A.
AU - Tseng, Chieh
AU - Leung, Cheuk Hong
AU - Yuan, Ying
AU - Karp, Daniel D.
AU - Subbiah, Vivek
AU - Hong, David
AU - Fu, Siqing
AU - Naing, Aung
AU - Rodon, Jordi
AU - Javle, Milind
AU - Ajani, Jaffer A.
AU - Raghav, Kanwal P.
AU - Somaiah, Neeta
AU - Mills, Gordon B.
AU - Tsimberidou, Apostolia M.
AU - Zheng, Xiaofeng
AU - Chen, Ken
AU - Meric-Bernstam, Funda
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41698-024-00634-6
DO - 10.1038/s41698-024-00634-6
M3 - Article
C2 - 39085400
AN - SCOPUS:85200251399
SN - 2397-768X
VL - 8
JO - npj Precision Oncology
JF - npj Precision Oncology
IS - 1
M1 - 166
ER -