TALAPRO-2: Final OS After First-Line Treatment for Patients With mCRPC

Talazoparib plus enzalutamide (tala/enza) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with standard-of-care enza alone as a first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) unselected for homologous recombination repair (HRR) gene alterations, according to the latest data presented on the TALAPRO-2 study.

Neeraj Agarwal, MD, FASCO, of the Huntsman Cancer Institute at the University of Utah, presented the final OS data as a late-breaking abstract at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.

The phase III TALAPRO-2 study initially met its primary endpoint, showing improved radiographic progression-free survival (rPFS) for tala/enza versus placebo plus enza as a first-line treatment for patients with mCRPC unselected for HRR gene alterations. In cohort 1, patients were randomized (1:1) to receive enza (160 mg) plus either tala (0.5 mg or 0.35 mg if moderate renal impairment was present) or placebo once daily. Patients were stratified by prior abiraterone or docetaxel treatment for castration-sensitive prostate cancer and HRR gene alteration status. Among the key eligibility criteria were asymptomatic or mildly symptomatic mCRPC, Eastern Cooperative Oncology Group performance status of ≤1, ongoing androgen deprivation therapy, and no prior life-prolonging therapy for CRPC.

For statistical significance at the final OS analysis, researchers noted that the stratified log-rank 2-sided P value needed to be ≤.022 using a group sequential design with O’Brien-Fleming spending function.

At the data cutoff of September 3, 2024, 52% of patients in the tala/enza arm and 60% of the patients in the placebo plus enza arm had died. The median follow-up was 52.5 months and 53.0 months, respectively.

The hazard ratio (HR) for OS was 0.796 (95% CI, 0.661-0.958; 2-sided P=.0155). The median OS was 45.8 months versus 37.0 months, respectively. In prespecified subgroup analyses, tala/enza led to more favorable OS in patients who were HRR deficient (n=169; HR, 0.549; 95% CI, 0.364-0.826; P=.0035) or HRR–non-deficient/unknown (n=636; HR, 0.878; 95% CI, 0.713-1.080; P=.218).

In exploratory analyses of patients with results available for both circulating tumor DNA and tumor tissue, Dr. Agarwal and colleagues found that OS favored tala/enza in patients without BRCA1/2 alterations (n=439; HR, 0.749; 95% CI, 0.582-0.963; P=.024) and in patients without HRR alterations (n=314; HR, 0.782; 95% CI, 0.582–1.050; P=.101).

Furthermore, they reported that the updated rPFS data also favored tala/enza (HR, 0.667; 95% CI, 0.551-0.807; P<.0001). The median rPFS was 33.1 months versus 19.5 months for patients in the placebo-plus-enza arm, respectively.

“Tala/enza demonstrated a statistically significant and clinically meaningful improvement in OS versus standard-of-care enza as first-line treatment in patients with mCRPC unselected for HRR gene alterations,” Dr. Agarwal and colleagues concluded, adding that “rPFS continues to favor tala/enza.”

No new safety signals were identified in this updated analysis, they noted.