Single agent PARP inhibitors have not been evaluated in untreated BRCA mutation carriers with early stage breast cancer. Concerns over efficacy and delay of initiation of chemotherapy may inhibit accrual in the neoadjuvant setting. In this pilot study, we evaluated if patients (pts) would accrue to a non-chemotherapy as their first treatment and if the toxicity profile would be acceptable.
The study was approved by the Institutional Review Board. Eligibility included > 1 cm tumor and germline BRCA mutation. HER2+ tumors were excluded. Pts underwent a pre-treatment biopsy, 2 months of talazoparib, off-study core biopsy, anthracycline and taxane-based chemotherapy +/-carboplatin, followed by surgery. Ultrasound tumor evaluations by dedicated breast ultrasonographers were obtained at baseline, 1 and 2 months. Success was defined if 20 patients could be accrued within 2 years and
Thirteen pts (BRCA1 + =10; BRCA2 + =3) participated from 08/2015 – 03/2016. Median age was 40 years (25-55). Eight had hormone receptor- and 4 had hormone receptor+ breast cancer, and 1 metaplastic. Two had clinical stage III, 9 had clinical stage II, and 2 had clinical stage I cancers. Decreases in tumor volume occurred in all 13 patients following 2 months of talazoparib monotherapy. The average volume loss was 78% (range 30-98%). Talazoparib was well tolerated with no grade 4 toxicities and only one patient requiring dose reduction due to grade 3 neutropenia. Common toxicities were neutropenia (n = 11), anemia (n = 8), nausea (n = 7), dizziness (n = 8) and fatigue (n = 8), which were grade 1, except: neutropenia (grade 2 = 4; grade 3 = 3) and grade 2 anemia or thrombocytopenia (n = 1 each). To date, pts have had no difficulty with transition to chemotherapy.
Given the profound clinical response with only 2 months of therapy and favorable toxicity profile, this pilot study was discontinued early after 13 pts accrued within 8 months at a single institution and 0 incidences of grade IV toxicity. An expansion cohort to estimate pathologic response to talazoparib alone with 4-6 months is underway.
Clinical trial identification
Legal entity responsible for the study
The University of Texas MD Anderson Cancer Center
MD Anderson Moonshot, Wolff-Toomim Fund. Drug only was provided by Biomarin and then Medivation once the drug was purchased by Medivation
J.K. Litton: I currently have research funding from Medivation, Genentech, Novartis and formerly from Biomarin; as the Principal Investigator of ongoing trials at my institution. No personal compensation.
All other authors have declared no conflicts of interest.