Subscribe

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive:

Talzenna Received a New Indication, With Enzalutamide, for Metastatic Castration-Resistant Prostate Cancer With HRR Gene Mutation

JHOP - August 2023 Vol 13, No 4 - FDA Oncology Update
NEW INDICATIONS

On June 20, 2023, the FDA approved a new indication for talazoparib (Talzenna; Pfizer), an oral poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with enzalutamide for homologous recombination repair (HRR) gene mutation–positive, metastatic castration-resistant prostate cancer (CRPC). The FDA granted this application priority review.

This is the first PARP inhibitor approved for use with a current standard of care (enzalutamide) for adults with metastatic CRPC and HRR gene mutation.

Talazoparib was initially approved as monotherapy for locally advanced or metastatic HER2-negative breast cancer with deleterious or suspected deleterious germline BRCA mutation.

The current approval was based on the results of the phase 3 TALAPRO-2 (NCT03395197) study, a randomized, double-blind, placebo-controlled, multicohort clinical trial of patients with metastatic CRPC and HRR gene mutation. These patients were randomized 1:1 to enzalutamide 160 mg daily plus talazoparib 0.5 mg or placebo daily.

The eligibility criteria included having a previous orchiectomy or receiving gonadotropin-releasing hormone (GnRH) analogs. Patients were excluded if they had previous systemic therapy for metastatic CRPC, but previous treatment with cytochrome (CY) P17 inhibitors or docetaxel for metastatic castration-sensitive prostate cancer was permitted. The trial stratified randomization by previous treatment with a CYP17 inhibitor or docetaxel.

The study investigators prospectively assessed multiple HRR genes using circulating tumor DNA–based next-generation sequencing assays and/or tumor tissue.

There was a significant improvement in radiographic progression-free survival (PFS), which was the major efficacy measure, for talazoparib with enzalutamide compared with placebo plus enzalutamide in patients with the HRR mutation (median, not reached vs 13.8 months; hazard ratio, 0.45; 95% confidence interval [CI], 0.33-0.61; P<.0001). According to the results of an exploratory analysis by BRCA mutation status, the hazard ratio for radiographic PFS was 0.20 (95% CI, 0.11-0.36) in patients with metastatic CRPC and the BRCA mutation (n=155) and 0.72 (95% CI, 0.49-1.07) in patients who had HRR-positive metastatic CRPC without the BRCA mutation.

The most common (≥10%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin, decreased neutrophils, decreased lymphocytes, fatigue, decreased platelets, decreased calcium, nausea, decreased appetite, decreased sodium, decreased phosphate, fractures, decreased magnesium, dizziness, increased bilirubin, decreased potassium, and dysgeusia. In TALAPRO-2, 39% of the total patients with metastatic CRPC who received talazoparib plus enzalutamide (199/511) needed a blood transfusion, including 22% who needed multiple transfusions, and 2 patients were diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy….For patients with [metastatic] CRPC harboring HRR genetic alterations, outcomes are even worse,” said Neeraj Agarwal, MD, FASCO, Professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, University of Utah, and global lead study investigator. “The FDA’s approval of the talazoparib and enzalutamide combination…represents a treatment option deserving of excitement and attention.”

The recommended dose of talazoparib is 0.5 mg orally, once daily, with enzalutamide (recommended dose, 160 mg orally once daily) until disease progression or unacceptable adverse events. This combination treatment should be accompanied by a concurrent GnRH analog or previous bilateral orchiectomy.

Related Items
Gavreto Received Regular FDA Approval for Patients With Non–Small Cell Lung Cancer and RET Gene Fusion
Online First published on September 8, 2023 in FDA Oncology Update
FDA Accelerated the Approval of Akeega, First and Only Dual-Action Tablet for Metastatic Prostate Cancer With BRCA Mutation
Online First published on September 8, 2023 in FDA Oncology Update
FDA Granted Accelerated Approval to Elrexfio, a Bispecific BCMA-Directed CD3 T-Cell Engager, for Relapsed or Refractory MM
Online First published on September 8, 2023 in FDA Oncology Update
Hepzato Kit FDA Approved as a Liver-Directed Treatment for Uveal Melanoma With Hepatic Metastases
Online First published on September 8, 2023 in FDA Oncology Update
FDA Accelerated the Approval of Talvey, First Bispecific GPRC5D-Directed CD3 T-Cell Engager, for Relapsed or Refractory MM
Online First published on September 8, 2023 in FDA Oncology Update
FDA Accelerated the Approval of Columvi for Selected Relapsed or Refractory Large B-Cell Lymphomas
JHOP - August 2023 Vol 13, No 4 published on August 17, 2023 in FDA Oncology Update
Lonsurf Received a New Indication, in Combination With Bevacizumab, for Previously Treated Metastatic Colorectal Cancer
JHOP - August 2023 Vol 13, No 4 published on August 7, 2023 in FDA Oncology Update
Jemperli Plus Chemotherapy Now FDA Approved for Front-Line Treatment of dMMR or MSI-H Endometrial Cancer
JHOP - August 2023 Vol 13, No 4 published on August 4, 2023 in FDA Oncology Update
Vanflyta Now Approved for Newly Diagnosed FLT3-ITD–Positive AML
JHOP - August 2023 Vol 13, No 4 published on July 28, 2023 in FDA Oncology Update
Epkinly FDA Approved for Relapsed or Refractory Diffuse Large B-Cell Lymphoma or High-Grade B-Cell Lymphoma
JHOP - June 2023 Vol 13, No 3 published on June 5, 2023 in FDA Oncology Update
© Amplity Health. All rights reserved.