This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.
The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5 mg (0.35 mg, moderate renal impairment) and enzalutamide 160 mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment.
In the all-comers (n = 398) and HRR-deficient populations (n = 198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9 % and 66.2 % of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7 % and 40.9 %, respectively), neutropenia (18.3 % and 18.7 %), and thrombocytopenia (7.3 % and 7.1 %). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8 % and 10.1 % of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1 % and 57.6 %), reduction (52.8 % and 52.0 %), hematologic supportive care (13.1 % and 10.6 %), and packed red blood cell transfusions (39.2 % and 35.9 %).
Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.
NCT03395197.
European journal of cancer (Oxford, England : 1990). 2024 Oct 20 [Epub ahead of print]
Arun A Azad, Karim Fizazi, Nobuaki Matsubara, Fred Saad, Ugo De Giorgi, Jae Young Joung, Peter C C Fong, Robert J Jones, Stefanie Zschäbitz, Jan Oldenburg, Neal D Shore, Curtis Dunshee, Joan Carles, Andre P Fay, Xun Lin, Liza DeAnnuntis, Nicola Di Santo, Michael A Zielinski, Neeraj Agarwal
Peter MacCallum Cancer Centre, Melbourne, Australia. Electronic address: ., Institut Gustave Roussy, University of Paris-Saclay, Villejuif, France., National Cancer Center Hospital East, Chiba, Japan., Division of Urology, Centre Hospitalier de l'Université de Montréal (CHUM/CRCHUM), Montréal, QC, Canada., IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy., National Cancer Center, Goyang, Republic of Korea., Auckland City Hospital and University of Auckland, Auckland, New Zealand., School of Cancer Sciences, University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK., National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Heidelberg, Germany., Akershus University Hospital (Ahus), Lørenskog, Norway., Carolina Urologic Research Center, Myrtle Beach, SC, USA., Arizona Urology Specialists, Tucson, AZ, USA., Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., PUCRS School of Medicine, Porto Alegre, Brazil., Pfizer Inc., La Jolla, CA, USA., Pfizer Inc., Collegeville, PA, USA., Formerly of Pfizer Inc., Durham, NC, USA., Huntsman Cancer Institute (NCI-CCC), University of Utah, Salt Lake City, UT, USA.