FDA Approves Talazoparib In Combination With Enzalutamide for mCRPC

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Oncology Nursing NewsAugust 2023

The PARP inhibitor talazoparib has been approved in combination with enzalutamide for the treatment of adult patients with homologous recombination repair gene–mutated metastatic castration-resistant prostate cancer.

The FDA has approved talazoparib (Talzenna) in combination with enzalutamide (Xtandi) for the treatment of adult patients with homologous recombination repair (HRR)-mutated metastatic castration-resistant prostate cancer (mCRPC). The approval is based on data from the phase 3 TALAPRO-2 trial (NCT03395197).1,2

The median radiographic progression-free survival (rPFS) with talazoparib/enzalutamide was not estimable (NE) (95% CI, 21.9-NE) vs 13.8 months (95% CI, 11.0-16.7) with placebo/enzalutamide (HR, 0.45; 95% CI, 0.33-0.61; P < .0001).1,2

Investigators of TALAPRO-2 assessed for one of the following HRR gene mutations before randomly assigning patients to an investigative or control arm: ATM, ATR, BRCA1/2, DK12, CHECK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C. These were identified using tissue-based or circulating tumor DNA assays.2 Prior to enrollment it was also required that patients had undergone prior orchiectomy or received gonadotropin-releasing hormone (GnRH) analogs if the procedure was not completed. Additionally, patients must have experienced disease progression on androgen deprivation therapy.1,2

The radiographic progression-free survival (rPFS) with talazoparib/enzalutamide was not estimable (NE) (95% CI, 21.9-NE) vs 13.8 months (95% CI, 11.0-16.7) with placebo/enzalutamide (HR, 0.45; 95% CI, 0.33-0.61; P < .0001).

Findings from TALAPRO-2 also showed that when stratified by BRCA status, patients with BRCA-mutant mCRPC had a median rPFS of NE (95% CI, NE-NE) vs 11.0 months (95% CI, 8.3-11.1) with talazoparib vs placebo, respectively (HR, 0.20; 95% CI, 0.11-0.36). Those with non–BRCA-mutated mCRPC had a median rPFS of 24.7 months (95% CI, 16.4-NE) vs 16.7 months (95% CI, 13.8-27.7) with the investigative and control regimens, respectively (HR, 0.72; 95% CI, 0.49-1.07).2

The recommended starting dose of talazoparib is 0.5 mg once daily in combination with enzalutamide at a recommended starting dose of 160 mg taken orally once daily and with a GnRH analog unless bilateral orchiectomy.

Dose reductions are permitted to manage adverse effects (AEs) and include the following guidelines: first dose reduction 0.35 mg once daily; second dose reduction 0.25 mg once daily; and third dose reduction 0.1 mg once daily.

Commonly reported AEs included fatigue, nausea, fractures, dizziness, and dysgeusia. The label comes with warning and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity.1

References

  1. FDA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer. FDA. June 20, 2023. Accessed June 20, 2023. bit.ly/3NE2Zgt
  2. Talzenna. Prescribing information. Pfizer Inc, 2023. Accessed June 20, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/211651s010lbl.pdf
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