A PARP inhibitor significantly increases progression-free survival over physician’s choice of therapy in a randomized phase III trial of patients with advanced breast cancer and a germline BRCA mutation.

A highly potent, dual-mechanism PARP inhibitor.

Inhibits PARP enzymes with increased formation of PARP-DNA complexes that result in DNA damage, apoptosis and cell death.

It prevents the repair of DNA damage, and results in cell death.

FDA Approves Talazoparib for BRCA-Mutated, HER2-Negative Breast Cancer

A PARP inhibitor approved for patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer.

Talzenna is the trade name.

BRACAnalysis CDx is the companion diagnostic test.

Approval based on phase III EMBRACA trial, in which it reduced the risk of disease progression or death by 46% versus chemotherapy in patients with BRCA-positive advanced breast cancer.

In the study, 431 patients with germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer, previously treated with chemotherapy were randomized in a 2:1 ratio to receive 1 mg daily of oral talazoparib or physician’s choice of chemotherapy.

All patients were required to have received no more than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease.

Results demonstrated that, at a median follow-up of 11.2 months, the median PFS was 8.6 months in the talazoparib arm and 5.6 months in the chemotherapy arms, respectively, and the ORR was 62.6% versus 27.2%, respectively.

The median duration of treatment was 6.1 months versus 3.9 months for talazoparib versus chemotherapy, respectively.

The complete response (CR) rate in the talazoparib arm was 5.5%, the partial response (PR) rate was 57.1%, and the stable disease rate was 21.0%: The corresponding rates in the chemotherapy arm were 0, 27.2%, and 31.6%, respectively.

Associated with a 24% reduction in the risk of death.

Has warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity.

Moderately emetogenic.

Most common adverse events associated with fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, and decreased appetite.

In a phase II study showed encouraging efficacy in patients with BRCA1/2 mutations.

Objective response rate 62.6% with talazoparib and 27.2% with physician’s choice, for an odds ratio of 4.99

Almost half of talazoparib patients (49.0%) had a grade 3 hematologic adverse event.

EMBRACA is the largest randomized trial evaluating a PARP inhibitor in patients with advanced breast cancer and a germline BRCA1/2 mutation.

Talozoparib shows durable antitumor activity in men with advanced metastatic castrate resistant prostate cancer with DDR-homologous recombination repair gene alterations.

FDA has approved talazoparib (Talzenna) plus enzalutamide (Xtandi) for use in patients with homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer (mCRPC).

TALAPRO-2 trial (NCT03395197), in which the addition of Talazoparib to enzalutamide significantly improved radiographic progression-free survival (rPFS) over enzalutamide alone in this population.

The median rPFS was not yet reached (95% CI, 21.9-not evaluable) in the investigative arm vs 13.8 months (95% CI, 11.0-16.7) with enzalutamide alone.


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