At the 2022 San Antonio Breast Cancer Symposium, Neelima Vidula, MD, Massachusetts General Hospital, Boston, MA, discusses the ongoing phase 2 trial evaluating the efficacy of the PARP inhibitor talazoparib for somatic BRCA-mutant, HER2-negative metastatic breast cancer.

Dr Vidula explained that in addition to investigating PARP inhibition in this population, the study is also collecting cell-free DNA once a month to observe the impact of any reversion mutations and attempt to identify emergent novel mutations that may contribute to treatment resistance. The study is currently enrolling, with an accrual goal of 30 patients.

Transcript

Hello, I'm Neelima Vidula. I'm a breast oncologist at Mass General Cancer Center. We had the privilege of presenting a trials-in-progress poster yesterday on our ongoing clinical study that is evaluating talazoparib, a PARP inhibitor, in patients with somatic BRCA-mutant metastatic breast cancer. This is an investigator-initiated study that is funded through the generosity of a Pfizer ASPIRE Award and also a Conquer Cancer Foundation of ASCO Breast Cancer Research Foundation Grant. In this study, we are evaluating talazoparib in patients who have metastatic breast cancer with a somatic BRCA1/2 mutation.

Talazoparib is approved by the Food and Drug Administration in the setting of germline BRCA1/2-mutant metastatic breast cancer. However, germline BRCA mutations account for 5% to 10% of breast cancer. Although PARP inhibitors are well tolerated oral targeted therapies, this limits the applicability in the current setting. Our study is aiming to help expand the population of patients who might potentially benefit from a PARP inhibitor.

We previously presented some work at the 2017 San Antonio Spotlight Discussion session and followed up with a publication in Clinical Cancer Research where we demonstrated that a portion of patients with metastatic breast cancer have somatic BRCA1/2 mutations. These are mutations that are shed by the tumor as opposed to germline mutations, which are mutations that patients are born with that can be identified using cell-free DNA, liquid biopsy assays, or tumor tissue genotyping assays. In conjunction with Dr Daniel Haber's laboratory at Mass General Cancer Center, we demonstrated, using a circulating tumor cell line derived from a patient who had a somatic BRCA mutation found in a blood-based assay, the efficacy of a PARP inhibitor in the laboratory.

Based on that study, we've developed this ongoing phase 2 trial that is evaluating talazoparib in patients who have somatic BRCA-mutant metastatic HER2-negative breast cancer. This is a multi-center trial that is being run at Mass General Cancer Center, also at Northwestern, MD Anderson, the University of California-San Francisco, Emory, Vanderbilt, and Cornell. In this study, patients who are found to have a somatic BRCA mutation, either in a cell-free DNA assay or a tumor tissue genotyping assay, who don't have a known germline mutation in the BRCA genes are eligible to participate in the study, and they're treated with talazoparib until the time of progression.

Our primary endpoint is to evaluate the progression-free survival in patients who are treated in this study, but we also have several exciting correlative endpoints. We're collecting cell-free DNA on a monthly basis to identify novel mutations that may emerge with treatment that might contribute to resistance, and we're also looking at the impact of reversion mutations that are present in baseline cell-free DNA and the response to the PARP inhibitor. This is a study that may potentially help expand the population of patients that could benefit from talazoparib, so we're really excited about it. It's ongoing. We currently have 8 patients enrolled, and we're aiming to enroll a total of 30 patients, so we really appreciate referrals from patients and providers that are interested in this study. Thank you.

Source:

Vidula N, Damodaran S, Blouch EL, et al. “Phase II study of talazoparib, a PARP inhibitor, in somatic BRCA1/2 mutant metastatic breast cancer identified by cell-free DNA or tumor tissue genotyping.” Presented at San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Poster OT1-11-01