Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as an initial treatment in unselected patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) in the China cohort of the phase 3 TALAPRO-2 trial.
Year: 2025
Type: conference-abstract
Abstract: 5047 Background: In the China cohort of the TALAPRO-2 study, unselected pts with mCRPC who received TALA + ENZA had improved radiographic progression-free survival per BICR (rPFS; HR=0.30; 95% CI, 0.17–0.56; P <0.0001; data cutoff: Nov 15, 2023), consistent with the global population (HR=0.63; 95% CI, 0.51–0.78; P <0.0001; data cutoff: Aug 16, 2022). In final prespecified analyses, TALA + ENZA significantly improved OS vs PBO + ENZA in the global population. Here we report final OS, a descriptive update of rPFS, and an extended follow-up of secondary outcomes in the China cohort. Methods: The China cohort includes pts from the unselected cohort 1 of TALAPRO-2 and China extension (unselected homologous recombination repair [HRR] gene status). Pts had asymptomatic/mildly symptomatic mCRPC, received ongoing androgen deprivation therapy, and were prospectively tested for HRR alterations in tumor tissue. Pts were randomized 1:1 to TALA 0.5 mg/day (moderate renal impairment 0.35 mg/day) or placebo (PBO); all pts received ENZA 160 mg/day. Primary endpoint was rPFS by BICR. OS was a key secondary endpoint. Other secondary endpoints included BICR-assessed objective response rate (ORR), time to prostate-specific antigen (PSA) progression, safety, and pt-reported outcomes. All reported P values are 2-sided. Results: Overall, 125 pts were randomized (TALA + ENZA, 63; PBO + ENZA, 62). At data cutoff (Sep 3, 2024; median follow-up, 33.2 mo in both arms) 35 pts (56%) in the TALA + ENZA arm and 41 pts (66%) in the PBO + ENZA arm had died. Clinically meaningful benefit in OS with TALA + ENZA vs PBO + ENZA was observed: HR=0.591 (95% CI, 0.369–0.944; P =0.0262); median OS (95% CI), 36.9 mo (21.7–42.4) vs 24.1 mo (16.8–30.5), respectively. Updated rPFS by BICR continued to favor TALA + ENZA vs PBO + ENZA (HR=0.312; 95% CI, 0.173–0.561; P <0.0001, median rPFS, 33.3 vs 10.5 mo, respectively). TALA + ENZA was favored vs PBO + ENZA in ORR by BICR (50% vs 32%, respectively; P =0.2845) and time to PSA progression (HR=0.540; 95% CI, 0.298–0.976; P =0.0411). Consistent with global and China cohort primary results, the most common grade ≥3 treatment-emergent adverse events (TEAEs) with TALA + ENZA were anemia (57%) and neutropenia (32%). TEAEs were generally manageable; 14 pts (22%) discontinued TALA due to TEAEs. No clinically meaningful between-arm differences were observed in global health status/quality of life (QoL) measured by EORTC QLQ-C30, except for role functioning, which favored TALA + ENZA. Conclusions: At extended follow-up, initial treatment with TALA + ENZA resulted in clinically meaningful improvement in OS, rPFS by BICR, and secondary efficacy endpoints vs PBO + ENZA in unselected pts with mCRPC in the TALAPRO-2 China cohort. No new safety signals were identified; QoL was maintained. Clinical trial information: NCT03395197 .
Source: Journal of Clinical Oncology
Institutions: Fudan University, Fudan University Shanghai Cancer Center, West China Hospital of Sichuan University, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking University Cancer Hospital, Second Affiliated Hospital of Soochow University, Suzhou University, Wuhan Union Hospital, Huazhong University of Science and Technology, Ningbo University, Ningbo University Affiliated Hospital, First Affiliated Hospital of Nanchang University, First Affiliated Hospital of Wenzhou Medical University, Second Hospital of Tianjin Medical University, Tianjin Medical University, Beijing Hospital, First Affiliated Hospital of Xi'an Jiaotong University, Zhejiang Provincial People's Hospital, Chongqing University, Chongqing Cancer Hospital, Nantong Tumor Hospital, Zhongshan Hospital, Pfizer (China)
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Pfizer
OpenAlex ID: W4410811617