KEY TAKEAWAYS
- The phase II trial aimed to test the effectiveness of talazoparib in pts with MBC with a somatic pathogenic BRCA1/2 mutation.
- The primary endpoint is PFS, while the secondary endpoint is ORR.
- The correlative endpoints include tracking BRCA1/2 mutant allele fraction changes and genomic evolution. The study is currently recruiting pts at Massachusetts General Hospital.
Poly (ADP-ribose) polymerase (PARP) inhibitors are currently approved for patients(pts) with germline BRCA1/2 mutated MBC, but only 5-10% of breast cancer pts have germline BRCA1/2 mutations. Researchers aimed to test the effectiveness of talazoparib, a PARP inhibitor, in pts with MBC with a somatic pathogenic BRCA1/2 mutation.
The study included pts who may have either triple-negative breast cancer with at least one prior chemotherapy regimen or hormone receptor-positive, HER2-negative breast cancer with at least one prior hormone therapy for metastatic breast cancer. Prior platinum therapy was allowed, provided there was no progression on platinum chemotherapy. Pts must not have a known germline BRCA1/2 mutation. Treatment will include daily administration of talazoparib at a 1 mg dose until disease progression, unacceptable toxicity, or consent withdrawal. Pts will have monthly clinical exams, scans (CT chest, abdomen, pelvis, and bone scan as appropriate) every 3 months, and monthly collection of circulating free DNA (cfDNA).
The primary endpoint is to measure the progression-free survival (PFS) based on RECIST 1.1 criteria. The study follows a 2-stage design to show that the treatment leads to “success” (PFS > 12 weeks) in at least 53% of pts, with 80% statistical power and a significance level of 4%. Secondary endpoints are the objective response rate (ORR) and toxicity using NCI CTCAE version 5.0. The study will also examine correlative endpoints such as changes in BRCA1/2 mutant allele fraction, genomic evolution, including the emergence of BRCA reversion mutations, and how biomarker changes affect outcomes.
The study is being conducted at Massachusetts General Hospital to see if PARP inhibitors can help more pts with breast cancer. If the study is successful, this could expand the number of people benefitting from this treatment.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.TPS1113
Clinical Trial: https://clinicaltrials.gov/study/NCT03990896
Neelima Vidula, Nora K. Horick, Erica Blouch, Amalia Rivera, Erin Basile, Ruth Fax, Leif W. Ellisen, Hope S. Rugo, and Aditya Bardia. DOI: 10.1200/JCO.2020.38.15_suppl.TPS1113 Journal of Clinical Oncology 38, no. 15_suppl.
