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

Abstract

BACKGROUND:

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.

OBJECTIVE:

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.

DESIGN, SETTING, AND PARTICIPANTS:

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.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

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.

RESULTS AND LIMITATIONS:

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.

CONCLUSIONS:

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.

PATIENT SUMMARY:

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.

• Authors: 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
• Journal: European urology (Eur Urol) Vol. 83 Issue 4 Pg. 352-360 (04 2023) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 35750582 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Pfizer, The Author(s). Published by Elsevier B.V. All rights reserved.

Chemical References

• talazoparib

Topics

• Male
• Humans
• Prostatic Neoplasms, Castration-Resistant (drug therapy, genetics, pathology)
• Quality of Life
• Pain
• Patient Reported Outcome Measures
• DNA Damage