TALAPRO-2 Data Support Approval of Talazoparib/Enzalutamide in HRR-Mutant mCRPC

Karim Fizazi, MD, a medical oncologist at Gustave Roussy and professor of oncology at the University of Paris-Saclay, discusses findings from the phase 3 TALAPRO-2 trial (NCT03395197) which support the recent FDA approval of talazoparib (Talzenna) plus enzalutamide (Xtandi) for the treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration resistant prostate cancer.

Data were presented by Fizazi at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, and showed that treatment with the combination achieved a statistically significant and clinically meaningful improvement in progression free survival (PFS) when used as a first-line therapy for this patient population.

Transcription:

0:09 | This trial is clearly positive. This is true for the all comer population with approximately a 30% reduction in the risk of progression or death, but it's even more true for patients with DNA repair defects, which is the population that I presented at ASCO. For these men, we saw a 55% reduction in the risk of radiographic progression or death, which is quite big. If you go into more detail and you focus on patients with BRCA alterations, either BRCA1 or BRCA2, there is about an 80% reduction in the risk of progression or death, which is enormous for these men and obviously very welcome.

1:07 | The other good news came potentially from patients with CDK12 alterations, and these patients also tend to benefit from the combination of the 2 drugs, while on the other hand, patients with ATM or CHEK2 to alterations do not seem to benefit from the combination. The FDA just made the decision to approve the drug in patients who benefit most, namely those with BRCA alterations.

1:39 | To be honest, it makes sense, at least at this stage, given that overall survival is immature in the overall population in the trial, and even for patients with DNA repair defects, these men when we analyzed the data, the majority was less than 25%. The majority of men were alive. Still, we see a clear signal with a 41% reduction in risk of death, not significant, but borderline, and this was an interim analysis. Probably in a year's time when we have a greater maturity of overall survival, the FDA will come back and look again at the data and see whether they confirm the approval only for patients with BRCA alterations, or whether they want to make the approval for a larger group of patients.