Leisha A. Emens, MD, PhD
STUDY DISCUSSANT Leisha A. Emens, MD, PhD, of Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University, Baltimore, entitled her remarks, “Target Practice in Triple-Negative Breast Cancer,” referring to the fact that there is currently no validated target in this aggressive breast cancer subtype. While concerted efforts are underway to identify targets, cytotoxic chemotherapy is currently the primary treatment choice, “and this represents a major unmet clinical need,” she said.
Emerging data indicate, however, that poly (ADP-ribose) polymerase (PARP) inhibitors may address this need. In fact, data from the OlympiAD study of olaparib (Lynparza) were presented in the ASCO Plenary Session this year. It showed a 42% reduction in progression overall and a 57% reduction in triple-negative patients receiving the PARP inhibitor.1 The agent evaluated in ABRAZO, talazoparib, is more potent than olaparib, Dr. Emens said.
It is now becoming evident that triple-negative breast cancer is not one subtype but has “substantial heterogeneity and overlap, including clinical subtypes, intrinsic subtypes, immune profiles, and mutational load,” she continued. “Traditional classification may result in overlooking highly effective therapy for a given patient.”
“But we are moving toward precision medicine, precisely characterizing molecular features of the disease in a way that can guide treatment,” she said. To this end, a number of potential molecular targets are being explored, including other genomic alterations (TP53 mutation, PTEN loss, MYC gain, INPP4B loss, RB1 mutation/ loss). Exploitation of the PIK3CA/Akt/mTOR pathway, genomic instability (which PARP inhibitors manipulate), epigenetic alterations, and immune activation pathways may also lend itself to future therapies. ■
DISCLOSURE: Dr. Emens is a consultant and on the advisory board for Celgene, Vaccinex, Amgen, AstraZeneca, Syndax, Peregrine, Bayer, ETHeRNA, Molecuvax, and Gritstone; has received research funding from Genentech, Roche, EMD Serone, MaxCyte, Merck, AstraZeneca, Aduro Biotech, and Corvus; and has received royalties from Aduro INC Licensing/vaccine. Dr. Burstein reported no conflicts of interest.
1. Turner NC, Telli ML, Rugo HS, et al: Final results of a phase 2 study of talazoparib following platinum or multiple cytotoxic regimens in advanced breast cancer patients with germline BRCA1/2 mutations (ABRAZO). 2017 ASCO Annual Meeting. Abstract 1007. Presented June 3, 2017.
“PARP inhibitors inhibit PARP catalytic activity and trap PARP at the sites of DNA damage. Cancers with mutations in BRCA1/2 are unable to repair trapped PARP, resulting in cell death.”— Nicholas C. Turner, MD
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