News >

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

Gina Columbus @ginacolumbusonc
Published: Tuesday, Oct 16, 2018

The FDA has approved talazoparib (Talzenna) for patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer, according to Pfizer, the manufacturer of the PARP inhibitor.

 
To be eligible for enrollment, patients were required to have received no more than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease. Moreover, patients must have received treatment with an anthracycline and/or a taxane, unless contraindicated, in the neoadjuvant, adjuvant, and/or metastatic setting. The primary endpoint was progression-free survival (PFS), as assessed by blinded independent central review. Secondary endpoints were overall survival (OS), safety, and overall response rate (ORR).

Results demonstrated that, at a median follow-up of 11.2 months, the median PFS was 8.6 months (95% CI, 7.2-9.3) in the talazoparib arm and 5.6 months (95% CI, 4.2-6.7) in the chemotherapy arms, respectively (HR, 0.54; 95% CI: 0.41-0.71; P <.0001). The ORR was 62.6% (95% CI, 55.8-69.0) versus 27.2% (95% CI, 19.3-36.3), respectively (odds ratio, 4.99; 95% CI, 2.9-8.8; 2-sided P value <.0001). The PFS benefit with talazoparib was observed across all predetermined patient subgroups.

Patient characteristics were mostly well balanced between the 2 arms, with a few variations of note. In the talazoparib arm, 63.4% of patients were aged <50 years, compared with 46.5% of patients in the control arm. Fifteen percent of patients receiving the PARP inhibitor had a history of CNS metastasis, compared with 13.9% in the chemotherapy group. In the talazoparib group, 37.6% of patients had a disease-free interval (initial diagnosis to advanced breast cancer) of under 12 months versus 29.2% in the chemotherapy arm.

The median duration of treatment was 6.1 months versus 3.9 months for talazoparib versus chemotherapy, respectively. Among patients with measurable disease, 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 physician’s choice arm were 0, 27.2%, and 31.6%, respectively.

The median duration of response was 5.4 months (95% CI, 4.2-6.3) with talazoparib and 3.1 months (95% CI, 2.8-5.6) with chemotherapy (HR, 0.43; 95% CI, 0.27-0.70; P = .0005). Moreover, the 1-year probability of sustained response was 23% vs 0%, respectively.

OS data are not yet mature; however, an interim OS analysis found a positive trend favoring talazoparib, with a 24% reduction in the risk of death. The median OS was 22.3 months (95% CI, 18.1-26.2) with the PARP inhibitor versus 19.5 months (95% CI, 16.3-22.4) with chemotherapy (HR, 0.76; 95% CI, 0.54-1.06; P = .105).
 
The indication for talazoparib includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity. The most common all-grade adverse events associated with fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, and decreased appetite.

The efficacy of BRACAnalysis CDx was based on the EMBRACA trial patient population for whom deleterious or suspected deleterious germline BRCA-mutated status was confirmed with either prospective or retrospective testing with BRACAnalysis CDx.

BRACAnalysis CDx is defined as an in vitro diagnostic device created for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Moreover, single nucleotide variants and small insertions and deletions are identified by polymerase chain reaction (PCR) and Sanger sequencing, while large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR.

BRACAnalysis CDx also has a diagnostic indication for the detection of deleterious or suspected deleterious mutations in BRCA1 and BRCA2 genes for patients with ovarian cancer to select therapy for olaparib (Lynparza) and/or rucaparib (Rubraca).

“Myriad’s BRACAnalysis CDx test was shown in the EMBRACA trial to accurately identify certain patients with a germline BRCA-mutation who may benefit from Talzenna,” said Johnathan Lancaster, MD, PhD, chief medical officer of Myriad Genetics. “It is important for patients to know their BRACAnalysis CDx results so they can fully understand their treatment options.”
 
Litton JK, Rugo HS, Ettl J, et al. A phase 3 trial comparing talazoparib, an oral PARP inhibitor, to physician’s choice of therapy in patients with advanced breast cancer and a germline BRCA-mutation. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract GS6-07.



... to read the full story
To Read the Full Story

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: How Do We Leverage PARP Inhibition Strategies in the Contemporary Treatment of Breast Cancer?May 31, 20191.5
Community Practice Connections™: A Better Way to Stop Pain: Paths Toward Responsible Postsurgical Pain Management for Patients With Breast CancerMay 31, 20191.5
Publication Bottom Border
Border Publication
x