Toxicities Associated With Talazoparib/Enzalutamide in HRR-Mutant mCRPC


Karim Fizazi, MD, discusses the toxicities seen with the combination of talazoparib plus enzalutamide.

Karim Fizazi, MD, a medical oncologist at Gustave Roussy and professor of oncology at the University of Paris-Saclay, discusses the toxicities seen with the combination of talazoparib (Talzenna) plus enzalutamide (Xtandi).

Recently, the FDA approved talazoparib in combination with enzalutamide for the treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration resistant prostate cancer based on findings from the phase 3 TALAPRO-2 trial (NCT03395197).

Here, Fizazi discusses some of the safety findings from the study and hope it may affect the use of this combination in clinical practice.


0:09 | 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.

0:53 | 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.

1:41 | 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.

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