Last month, Pfizer reported about its phase 3 TALAPRO-2 study in which the combination of the poly ADP-ribose polymerase (PARP) inhibitor Talzenna® (talazoparib) with the androgen receptor inhibitor Xtandi® (enzalutamide) was tested in men with metastatic castration-resistant prostate cancer (mCRPC). These results were presented during the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU). The data show a 37% reduction in the risk of disease progression or death when enzalutamide is combined with talazoparib, compared to placebo plus enzalutamide.
TALAPRO-2 enrolled a total of 1,095 patients with mCRPC and included two cohorts: 380 patients with homologous recombination repair mutations (HRR deficient) and 750 all-comers (HRR non-deficient or unknown).1 Subjects were randomised to receive enzalutamide in combination with either talazoparib or placebo.
In the radiographic progression-free survival (rPFS) analysis, talazoparib plus enzalutamide reduced the risk of disease progression or death by 37% versus placebo plus enzalutamide (HR[95%CI]: 0.63[0.51-0.78]; p< 0.001) among all subjects. The median rPFS for the treatment arm was not reached at the time of analysis and it was reported at 21.9 months for placebo plus enzalutamide.
Pfizer indicated that the study also showed a clinically meaningful improvement in the median rPFS for patients treated with talazoparib plus enzalutamide across the assessed subgroups: HRR-deficient (HR[95%CI]: 0.46[0.30-0.70]; p<0.001) and HRR-non-deficient or unknown (HR[95%CI]:0.70;[0.54-0.89]; p=0.004). Additionally, other disease progression parameters were significantly improved (p<0.05) in patients treated with talazoparib plus enzalutamide, such as objective response rates, prostate-specific antigen (PSA) response ≥50%, time to PSA progression, use of subsequent cytotoxic chemotherapy and antineoplastic therapy. The median time to definitive clinically meaningful deterioration in global health status/quality of life was longer in those treated with talazoparib plus enzalutamide as well (30.8 vs. 25.0 months, respectively; HR[95%CI]:0.78[0.62-0.99]; p=0.04).
Following these results, the FDA granted Priority Review for a supplemental new drug application to the talazoparib and enzalutamide combination for the treatment of men with mCRPC. Neither talazoparib nor the combination of talazoparib plus enzalutamide has been approved by any regulatory agency for the treatment of mCRPC. In addition to the TALAPRO-2 trial, the combination of talazoparib plus enzalutamide is being investigated in the phase 3 TALAPRO-3 trial, a global, randomised, double-blind, placebo-controlled phase 3 study in men with HRR-deficient metastatic castration-sensitive prostate cancer.2