Faculty Collaboration Database

Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations: TALAPRO-1 Safety Analyses. Oncologist 2022 Oct 01;27(10):e783-e795

Date

09/21/2022

Pubmed ID

36124924

Pubmed Central ID

PMC9526483

DOI

10.1093/oncolo/oyac172

Scopus ID

2-s2.0-85139536391 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

BACKGROUND: The phase II TALAPRO-1 study (NCT03148795) demonstrated durable antitumor activity in men with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). Here, we detail the safety profile of talazoparib.

PATIENTS AND METHODS: Men received talazoparib 1 mg/day (moderate renal impairment 0.75 mg/day) orally until radiographic progression, unacceptable toxicity, investigator decision, consent withdrawal, or death. Adverse events (AEs) were evaluated: incidence, severity, timing, duration, potential overlap of selected AEs, dose modifications/discontinuations due to AEs, and new clinically significant changes in laboratory values and vital signs.

RESULTS: In the safety population (N = 127; median age 69.0 years), 95.3% (121/127) experienced all-cause treatment-emergent adverse events (TEAEs). Most common were anemia (48.8% [62/127]), nausea (33.1% [42/127]), decreased appetite (28.3% [36/127]), and asthenia (23.6% [30/127]). Nonhematologic TEAEs were generally grades 1 and 2. No grade 5 TEAEs or deaths were treatment-related. Hematologic TEAEs typically occurred during the first 4-5 months of treatment. The median duration of grade 3-4 anemia, neutropenia, and thrombocytopenia was limited to 7-12 days. No grade 4 events of anemia or neutropenia occurred. Neither BRCA status nor alteration origin significantly impacted the safety profile. The median (range) treatment duration was 6.1 (0.4-24.9) months; treatment duration did not impact the incidence of anemia. Only 3 of the 15 (11.8% [15/127]) permanent treatment discontinuations were due to hematologic TEAEs (thrombocytopenia 1.6% [2/127]; leukopenia 0.8% [1/127]).

CONCLUSION: Common TEAEs associated with talazoparib could be managed through dose modifications/supportive care. Demonstrated efficacy and a manageable safety profile support continued evaluation of talazoparib in mCRPC.

CLINICALTRIALS.GOV IDENTIFIER: NCT03148795.

Author List

Mehra N, Fizazi K, de Bono JS, Barthélémy P, Dorff T, Stirling A, Machiels JP, Bimbatti D, Kilari D, Dumez H, Buttigliero C, van Oort IM, Castro E, Chen HC, Di Santo N, DeAnnuntis L, Healy CG, Scagliotti GV

Author

Deepak Kilari MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Anemia
Antineoplastic Agents
DNA Damage
Humans
Male
Neutropenia
Phthalazines
Poly(ADP-ribose) Polymerase Inhibitors
Prostatic Neoplasms, Castration-Resistant