(UroToday.com) The 2024 GU ASCO annual meeting featured a prostate cancer session and a presentation by Dr. Karim Fizazi discussing patient reported outcomes from the phase 3 TALAPRO-2 study cohort 2. Cohort 2 of the TALAPRO-2 study demonstrated benefit in radiographic progression-free survival with talazoparib plus enzalutamide (n = 200) vs placebo + enzalutamide (n = 199) across gene subgroups in men with HRR mutations receiving first-line treatment for metastatic castration resistant prostate cancer (mCRPC).1
The impact of treatment on patients’ health related quality of life is important to consider along with potential benefit for various HRR gene alterations because maintaining or improving health related quality of life is a major goal of treatment for mCRPC. This post-hoc analyses presented at GU ASCO 2024 aimed to understand patient reported outcomes by HRR gene clusters.
Patient reported outcomes were assessed on day 1 and scheduled visits (every 4 weeks until week 53, then every 8 weeks) until radiographic progression using the EORTC QLQ-C30 and PR25 and BPI-SF. Prespecified patient reported outcome endpoints included overall mean change from baseline (per longitudinal repeated measures mixed-effects model) and time to definitive deterioration with a clinically meaningful change of ≥10-points for the EORTC QLQ-C30. Stratified log-rank test and Cox proportional hazards model were used to make time for definitive deterioration between-arm comparisons.
Mutually exclusive gene clustering alteration dominance hierarchy was applied in the following order:
- Any BRCA1/2 alteration (BRCA mutation cluster)
- PALB2 (PALB2 cluster)
- CDK12 (CDK12 cluster)
- ATM (ATM cluster)
- Then any of all other HRR7 genes (MLH1, CHEK2, NBN, FANCA, ATR, RAD51C, MRE11A)
The patient reported outcomes population (n = 394) comprised 197 patients in each arm. There were 154 patients in the BRCA mutation cluster, 15 in the PALB2 mutation cluster, 71 patients in the CDK12 mutation cluster, 70 in the ATM mutation cluster, and 81 patients in the other gene cluster:
A significantly longer time to definitive deterioration in global health status/quality of life was observed for talazoparib + enzalutamide vs placebo + enzalutamide in the BRCA mutations (HR 0.54, 95% CI 0.29, 0.99; p = 0.043; median NE vs 19.0) and CDK12 clusters (HR 0.43, 95% CI 0.19, 0.98; p = 0.019, median 30.7 vs 16.6):
No statistically significant or clinically meaningful results were observed in the overall mean scores for global health status/quality of life between arms in all clusters, except in the PALB2 mutation cluster where placebo + enzalutamide was favored:
Time to deterioration in worse pain favored the talazoparib + enzalutamide arm, however, these findings were not statistically significant:
The mean difference in worst pain favored the talazoparib + enzalutamide group in the BRCA mutation cluster statistically, but did not meet the predefined clinically meaningful threshold of >=2 points:
Dr. Fizazi concluded his presentation discussing patient reported outcomes from the phase 3 TALAPRO-2 study cohort 2 with the following take-home points:
- Patient reported outcome findings by HRR gene clusters are consistent with radiographic progression-free survival benefit analyses by gene clusters, with the most benefit observed in BRCA and CDK12 mutations
- This was an exploratory posthoc analysis limited by missing patient reported outcome assessments and sample sizes, especially in the PALB2 cluster
Presented by: Karim Fizazi, MD, PhD, Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Paris, France
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Jan 25 – Sat, Jan 27, 2024.
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