Combination extends survival in metastatic prostate cancer
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The addition of talazoparib to enzalutamide extended OS among men with metastatic castration-resistant prostate cancer, according to the agent’s manufacturer.
Talazoparib (Talzenna, Pfizer) is an oral poly(ADP-ribose) polymerase (PARP) inhibitor. The agent is approved in the United States for single-agent treatment of certain patients with breast cancer, as well as in combination with enzalutamide (Xtandi; Astellas, Pfizer) for treatment of men with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer.
The randomized phase 3 TALAPRO-2 study included 1,035 men with metastatic castration-resistant prostate cancer who had not received systemic treatment after diagnosis of metastatic disease.
The study included two cohorts. One “all-comers” cohort included 805 men, 169 of whom had HRR mutations and 636 of whom did not. The second cohort included 399 men with HRR mutations, 169 of whom came from the first cohort and 230 of whom enrolled specifically in the second cohort.
Researchers assigned men to receive 160 mg enzalutamide daily plus either 0.5 mg talazoparib daily or placebo.
Radiographic PFS in both cohorts served as the primary endpoint. OS, objective response rate, duration of response and PSA response served as secondary endpoints.
Results of a final prespecified OS analysis showed a statistically significant improvement with the combination in both cohorts compared with enzalutamide alone.
A previously reported improvement in radiographic PFS persisted at the time of final analysis.
“These overall survival results indicate potentially practice-changing efficacy for Talzenna in combination with Xtandi for men with metastatic castration-resistant prostate cancer,” Neeraj Agarwal, MD, FASCO, global lead investigator for TALAPRO-2 and professor and presidential endowed chair of cancer research at Huntsman Cancer Institute at The University of Utah, said in a Pfizer press release. “Metastatic castration-resistant prostate cancer is the most advanced and aggressive stage of the disease, and the TALAPRO-2 results provide much-needed hope to patients who remain in high unmet need for effective treatment options.”
The safety profiles of talazoparib and enzalutamide appeared generally consistent with the established profiles of each therapy, according to the press release.
The most common adverse events reported among patients treated with the combination included decreased hemoglobin (79% for combination vs. 34% for enzalutamide alone), decreased neutrophils (60% vs. 18%), decreased lymphocytes (58% vs. 36%), fatigue (49% vs. 40%), decreased platelets (45% vs. 8%), decreased calcium (25% vs. 11%) and nausea (21% vs. 17%).
Serious adverse reactions included anemia (9%) and fracture (3%). Three trial participants developed fatal adverse reactions. These included one case each of sepsis, pneumonia and COVID-19 infection.
Complete results from TALAPRO-2 will be submitted for presentation at a medical meeting and shared with regulatory authorities to potentially support an expanded approved label for talazoparib, according to the release.
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