Dr. Alumkal on FDA approval of talazoparib/enzalutamide for HRR gene–mutated mCRPC

In this video, Joshi Alumkal, MD, discusses the FDA approval of the combination of talazoparib (Talzenna) and enzalutamide (Xtandi) for the treatment of patients with homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer.

Alumkal is Wicha Family Professor of Oncology, professor, Department of Internal Medicine, section head, Prostate and Genitourinary Medical Oncology, associate division chief, Basic Research, Division of Hematology-Oncology, member, the University of Michigan Rogel Cancer Center, director, Epigenetic Therapy, Michigan Center for Translational Pathology.

Video Transcript

Another PARP inhibitor that was recently approved this year is talazoparib, [which was approved in combination with enzalutamide] based on the randomized phase 3 TALAPRO-2 trial. This trial enrolled patients who had disease progression on androgen-deprivation therapy alone but who were naive to the androgen receptor inhibitor enzalutamide [and naive to all other second-generation androgen receptor inhibitors, as well]. Half of the patients were randomized to receive enzalutamide plus placebo and half of the patients were randomized to receive enzalutamide plus talazoparib. The trial was stratified by homologous recombination DNA repair (HRR) status, looking at a variety of genes, including BRCA1 and BRCA2, in addition to about 6 or 7 other genes. They also had a cohort of patients who either had unknown HRR status or who are negative for these alterations. Ultimately, they found that about 20% of patients had HRR defects, and the remainder were unknown status or did not have HRR defects.

The primary end point was radiographic progression-free survival. And they showed that there was an improvement with the combination oftalazoparib and enzalutamide in all comers, and specifically also in the HRR-positive cohort. There was much less of a benefit in the cohort that was HRR-negative or unknown status. And so based upon those results, the FDA approved the combination of talazoparib and enzalutamide in those patients who have castration-resistant prostate cancer who have not yet had enzalutamide and whose tumors harbor gene alterations that were included in the subset of patients with HRR defects.

Transcript has been edited for clarity.