Compared with standard-of-care enzalutamide as first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), the PARP inhibitor talazoparib plus the androgen receptor blocker enzalutamide yielded clinically meaningful and statistically significant improvement in radiographic progression-free survival (rPFS), the TALAPRO-2 trial shows. “Final overall survival data and additional long-term safety follow-up will further clarify the clinical benefit of the treatment combination in patients with and without tumour [homologous recombination repair (HRR)] gene alterations,” the investigators conclude.
In 26 countries in North America, Europe, Israel, South America, South Africa, and the Asia-Pacific region, participants were adult men with asymptomatic or mildly symptomatic mCRPC receiving ongoing androgen deprivation therapy. After prospective assessment for homologous recombination repair (HRR) gene alterations in tumor tissue, the men were randomized with HRR and previous life-prolonging treatment stratification to talazoparib 0.5 mg or placebo, plus enzalutamide 160 mg, administered orally once daily.
Based on a primary endpoint of rPFS in the intention-to-treat population, the investigators found: “Between Jan 7, 2019, and Sept 17, 2020, 805 patients were enrolled and randomly assigned (402 to the talazoparib group and 403 to the placebo group). Median follow-up for rPFS was 24.9 months (IQR 21.9–30.2) for the talazoparib group and 24.6 months (14.4–30.2) for the placebo group. At the planned primary analysis, median rPFS was not reached (95% CI 27.5 months–not reached) for talazoparib plus enzalutamide and 21.9 months (16.6–25.1) for placebo plus enzalutamide (hazard ratio 0.63; 95% CI 0.51–0.78; P <0.0001). In the talazoparib group, the most common treatment-emergent adverse events were anaemia, neutropenia, and fatigue; the most common grade 3–4 event was anaemia (185 [46%] of 398 patients), which improved after dose reduction, and only 33 (8%) of 398 patients discontinued talazoparib due to anaemia. Treatment-related deaths occurred in no patients in the talazoparib group and two patients (<1%) in the placebo group.”