Patient-reported Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Harboring DNA Damage Response Alterations Treated with Talazoparib: Results from TALAPRO-1.

Talazoparib has shown antitumor activity with a manageable safety profile in men with metastatic castration-resistant prostate cancer (mCRPC) and DNA damage response (DDR)/homologous recombination repair (HRR) alterations.

To evaluate patient-reported health-related quality of life (HRQoL) and pain in patients who received talazoparib in the TALAPRO-1 study, with a special interest in patients harboring breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations.

TALAPRO-1 is a single-arm, phase 2 study in men with mCRPC DDR alterations either directly or indirectly involved in HRR, who previously received one to two taxane-based chemotherapy regimens for advanced prostate cancer and whose mCRPC progressed on one or more novel hormonal agents.

Men completed the European Quality-of-life Five-dimension Five-level scale (EQ-5D-5L), EQ-5D visual analog scale (VAS), and Brief Pain Inventory-Short Form at predefined time points during the study. The patient-reported outcome (PRO) population included men who completed a baseline and one or more postbaseline assessments before study end. Longitudinal mixed-effect models assuming an unstructured covariance matrix were used to estimate the mean (95% confidence interval [CI]) change from baseline for pain and general health status measurements among all patients and patients with BRCA1/2 mutations.

In the 97 men in the PRO population treated with talazoparib (BRCA1/2, n = 56), the mean (95% CI) EQ-5D-5L Index improved (all patients, 0.05 [0.01, 0.08]; BRCA1/2 subset, 0.07 [0.03, 0.10]), as did the EQ-5D VAS scores (all patients, 5.42 [2.65, 8.18]; BRCA1/2 subset, 4.74 [1.07, 8.41]). Improvements in the estimated overall change from baseline (95% CI) in the mean worst pain were observed in all patients (-1.08 [-1.52, -0.65]) and the BRCA1/2 subset (-1.15 [-1.67, -0.62]). The probability of not having had experienced deterioration of worst pain by month 12 was 84% for all patients and 83% for the BRCA1/2 subset.

In heavily pretreated men with mCRPC and DDR/HRR alterations, talazoparib was associated with improved HRQoL in all patients and the BRCA1/2 subset. In both patient groups, worst pain improved from baseline and the probability of not experiencing a deterioration in worst pain with talazoparib was high.

We show that talazoparib was associated at least with no change or improvements in health-related quality of life (HRQoL) and pain burden in men with metastatic castration-resistant prostate cancer and DNA damage response/homologous recombination repair gene alterations in the TALAPRO-1 study. These findings in patient-reported HRQoL and pain complement the antitumor activity and tolerability profile of talazoparib.

European urology. 2022 Jun 21 [Epub ahead of print]

Fred Saad, Johann de Bono, Philippe Barthélémy, Tanya Dorff, Niven Mehra, Giorgio Scagliotti, Adam Stirling, Jean-Pascal Machiels, Vincent Renard, Marco Maruzzo, Celestia S Higano, Howard Gurney, Cynthia Healy, Helen Bhattacharyya, Bhakti Arondekar, Alexander Niyazov, Karim Fizazi

Division of Urology, Centre Hospitalier de l'Université de Montréal (CHUM/CRCHUM), Montreal, QC, Canada. Electronic address: ., The Institute of Cancer Research and Royal Marsden Hospital, London, UK., Medical Oncology Unit, Institut de Cancérologie Strasbourg Europe, Strasbourg, France., Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands., Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy., ICON Institute of Innovation and Research, ICON Cancer Centre, Chermside, QLD, Australia., Department of Medical Oncology, Institut Roi Albert II, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium., Medical Oncology Department, AZ Sint-Lucas, Ghent, Belgium., Department of Oncology, Istituto Oncologico Veneto, Padova, Italy., Department of Urologic Science, University of British Columbia, Vancouver, BC, Canada., Department of Medical Oncology, Westmead Hospital, Westmead, NSW, Australia., Department of Oncology, Pfizer Inc, Collegeville, PA, USA., Biostatistics and Data Management, Pfizer Inc, New York, NY, USA., Patient Health and Impact, Pfizer Inc, Collegeville, PA, USA., Patient Health and Impact, Pfizer Inc, New York, NY, USA., Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France.

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