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Ref Type Journal Article
PMID (39085400)
Authors Piha-Paul SA, Tseng C, Leung CH, Yuan Y, Karp DD, Subbiah V, Hong D, Fu S, Naing A, Rodon J, Javle M, Ajani JA, Raghav KP, Somaiah N, Mills GB, Tsimberidou AM, Zheng X, Chen K, Meric-Bernstam F
Title Phase II study of talazoparib in advanced cancers with BRCA1/2, DNA repair, and PTEN alterations.
Journal Vol Issue Date Pages Journal Short Title
NPJ precision oncology 8 1 2024 Jul 31 166 NPJ Precis Oncol
URL
Abstract Text 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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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
ATM S1599* appendix cancer predicted - sensitive Talazoparib Case Reports/Case Series Actionable In a Phase II trial, Talzenna (talazoparib) treatment resulted in a clinical benefit rate (CBR) of 22.8% (18/79, 1 complete and 7 partial responses, 10 with stable disease >/=24 weeks) in patients with advanced solid tumors harboring mutations in DNA damage repair genes, including a partial response lasting 12 weeks in an appendiceal cancer patient harboring ATM S1599* (PMID: 39085400; NCT02286687). 39085400
ATM G1676fs cholangiocarcinoma predicted - sensitive Talazoparib Case Reports/Case Series Actionable In a Phase II trial, Talzenna (talazoparib) treatment resulted in a clinical benefit rate (CBR) of 22.8% (18/79, 1 complete and 7 partial responses, 10 with stable disease >/=24 weeks) in patients with advanced solid tumors harboring mutations in DNA damage repair genes, including a partial response lasting 16 weeks in a cholangiocarcinoma cancer patient harboring ATM G1676fs (PMID: 39085400; NCT02286687). 39085400
PTEN loss Advanced Solid Tumor no benefit Talazoparib Phase II Actionable In a Phase II trial, Talzenna (talazoparib) treatment resulted in limited clinical benefit in patients with advanced solid tumors harboring PTEN deleterious mutations or loss (by IHC), with a clinical benefit rate of 9.4% (1/14, 1 with stable disease >/=24 weeks) and a median overall survival of 8.5 months and a median progression-free survival of 7.7 weeks (PMID: 39085400; NCT02286687). 39085400
PTEN inact mut Advanced Solid Tumor no benefit Talazoparib Phase II Actionable In a Phase II trial, Talzenna (talazoparib) treatment resulted in limited clinical benefit in patients with advanced solid tumors harboring PTEN deleterious mutations or loss (by IHC), with a clinical benefit rate of 9.4% (1/14, 1 with stable disease >/=24 weeks) and a median overall survival of 8.5 months and a median progression-free survival of 7.7 weeks (PMID: 39085400; NCT02286687). 39085400
PALB2 R170fs bladder urachal adenocarcinoma predicted - sensitive Talazoparib Case Reports/Case Series Actionable In a Phase II trial, Talzenna (talazoparib) treatment resulted in a clinical benefit rate (CBR) of 22.8% (18/79, 1 complete and 7 partial responses, 10 with stable disease >/=24 weeks) in patients with advanced solid tumors harboring mutations in DNA damage repair genes, including a partial response lasting 17 weeks in a urachal adenocarcinoma patient harboring PALB2 R170fs14 (PMID: 39085400; NCT02286687). 39085400