ASCO 2023: Patient-Reported Outcomes Among Men Receiving Talazoparib + Enzalutamide vs Placebo + ENZA as First-Line Treatment for mCRPC: Results from a Phase 3 Study (TALAPRO-2)

(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster discussion session. Dr. Neeraj Agarwal presented the patient-reported outcomes (PROs) from the TALAPRO-2 trial evaluating the combination of talazoparib + enzalutamide versus placebo + enzalutamide as 1st line treatment for mCRPC patients.

TALAPRO-2 is a phase III randomized, double-blind, placebo-controlled trial that evaluated the combination of talazoparib and enzalutamide in the 1^st line treatment setting for mCRPC patients. Patients were randomized 1:1 to talazopaarib 0.5 mg once daily (reduced dose from standard of 1.0 mg) plus enzalutamide 160 mg once daily versus placebo + enzalutamide. Similar to PROpel, this was a biomarker unselected cohort of ‘all comers’. The combination of talazoparib/enzalutamide was associated with a 37% decrease in the rPFS hazard, compared to placebo/enzalutamide (median: not reached versus 22 months; HR: 0.63, 95% CI: 0.51 – 0.78, p<0.001).

rPFS benefits were observed in both the HRR mutated and non-mutated subgroups. As expected, the magnitude of effect was larger in the HRR mutated (median rPFS: 28 versus 16 months; HR: 0.46, 95% CI: 0.30 – 0.70, p<0.001) versus non-mutated subgroup (HR: 0.66, 95% CI: 0.49 – 0.91, p=0.009). OS data remains immature, with a trend towards an overall survival (OS) improvement in the overall cohort (HR: 0.89, 95% CI: 0.69 – 1.14, p=0.35).

In this report, Dr. Agarwal and colleagues reported PROs from TALAPRO-2. PROs were assessed at baseline, at scheduled visits (every 4 weeks up to week 53, thereafter every 8 weeks) until progression, and at safety (at treatment discontinuation) and long-term follow-up visits. PRO instruments included the EORTC QLQ-C30 and its prostate cancer module, QLQ-PR25. BPI-SF and EQ-5D-5L were also collected, but not presented in this report. The mean change from baseline in individual domain scores was calculated using a longitudinal repeated measures mixed-effects model, with a threshold for clinically meaningful differences of ≥ 10 points. Time to definitive deterioration was summarized using Kaplan-Meier analysi. Treatment arms were compared using a stratified log-rank test and Cox proportional hazards modeling.

The TALAPRO-2 PRO cohort included 793 patients (intervention arm: 395; control arm: 398). The median patient age was 71 years and 62% were Caucasian.

Using the EORTC QLQ-C30, the time-to-definitive deterioration in global health status (GHS)/QoL was significantly longer with combination talazoparib plus enzalutamide, compared to placebo plus talazoparib (HR: 0.78, 95% CI: 0.62 – 0.99, p=0.038).

The treatment effect on estimated mean change in GHS/QoL score from baseline similarly favored the intervention arm, although the difference was not clinically meaningful. Furthermore, no significant difference in functional scales were observed between the two arms. There were no clinically meaningful differences in any of the individual symptom scales.

Using the EORTC QLQ-PR25 questionnaire, time-to-definitive deterioration of urinary symptoms was non-significantly prolonged in the intervention arm (HR: 0.76, 95% CI: 0.54 - 1.06, p=0.11). 

No significant differences were observed in any functional or symptom scales. 

The investigators concluded that compared with placebo/enzalutamide, the combination of talazoparib + enzalutamide may be associated with modest improvements in global health status and quality of life, although the differences were not clinically meaningful; otherwise, all functioning scale scores were similar across both arms. This study is limited by the secondary nature of the PRO endpoints, with no adjustments for comparison multiplicity performed and the poor post-treatment completion rates, limiting assessment of PROs in the post-treatment setting.

Presented by: Neeraj Agarwal, MD, Professor, Department of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.