Dr. Fizazi discusses the safety of talazoparib/enzalutamide in mCRPC

In this video, Karim Fizazi, MD, PhD, a medical oncologist at Gustave Roussy, Villejuif, France, discusses safety data for talazoparib (Talzenna) plus enzalutamide (Xtandi) from the phase 3 TALAPRO-2 trial,¹ which explored the combination in patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer. Based on the TALAPRO-2 trial, the FDA approved talazoparib/enzalutamide for use in this setting.²

Video Transcript

The main driver regarding toxicity is anemia. In the trial, we saw approximately 40% of grade 3 and 4 anemia with a combination of talazoparib and enzalutamide, which obviously is not nothing, so this is important clinically. Also because it means transfusion for many of these patients. Having said that, anemia or toxicity in general was rarely responsible for drug discontinuation, at least permanent discontinuation, meaning that we can adapt, patients and doctors. Of course transfusion and dose reduction can find their place and are probably helpful.

Also, of note in the trial, we allowed patients with existing anemia up to 9 grams. When you start with just 9 grams, you're likely to develop grade 3 or 4, and that does not necessarily mean that this is only drug-related, but it's unfortunately, cancer-related because they have bone marrow failure already. I'm glad that we enrolled these men because we want to show them that we can help them, even if they have severe cancers. Anemia is there, but it's mostly manageable.

We also saw thrombocytopenia and neutropenia in excess, but this was mostly a biological finding, not a clinical one, which is rare. Also, the degree of pulmonary embolism was very low, 2% vs 1%, and most importantly, we haven't seen a single case of myelodysplasia or leukemia. With a PARP inhibitor, you will need to be cautious, but I think this is super reassuring.

Transcript has been edited for clarity.

References

1. Fizazi K, Azad A, Matsubara N, et al. TALAPRO-2: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) + ENZA as first-line (1L) treatment for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene alterations. J Clin Oncol. 2023;5004(suppl 16). doi: 10.1200/JCO.2023.41.16_suppl.5004

2. Pfizer’s TALZENNA® in Combination with XTANDI® Receives U.S. FDA Approval. Accessed June 21, 2023. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-talzennar-combination-xtandir-receives-us-fda