Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations: TALAPRO-1 Safety Analyses.

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.

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.

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]).

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.

NCT03148795.

The oncologist. 2022 Sep 19 [Epub ahead of print]

Niven Mehra, Karim Fizazi, Johann S de Bono, Philippe Barthélémy, Tanya Dorff, Adam Stirling, Jean-Pascal Machiels, Davide Bimbatti, Deepak Kilari, Herlinde Dumez, Consuelo Buttigliero, Inge M van Oort, Elena Castro, Hsiang-Chun Chen, Nicola Di Santo, Liza DeAnnuntis, Cynthia G Healy, Giorgio V Scagliotti

Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands., Institut Gustave Roussy, University of Paris-Saclay, Villejuif, France., The Institute of Cancer Research and The Royal Marsden Hospital, London, UK., Medical Oncology, Institut de Cancérologie Strasbourg Europe, Strasbourg, France., Medical Oncology & Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA., ICON Cancer Centre, Queensland, Australia., Medical Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium., Medical Oncology 1 Unit, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy., Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA., Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, and Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium., Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy., Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands., Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain., Biostatistics, Pfizer Inc., La Jolla, CA, USA., Global Product Development, Pfizer Inc., Durham, NC, USA., Safety, Pfizer Inc., Collegeville, PA, USA., Oncology, Pfizer Inc., Collegeville, PA, USA.

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