Breast Cancer
Emanuel Petricoin, PhD
George Mason University
Summary:
For women with newly diagnosed Stage II/III breast cancer, achieving a complete pathological response in the neoadjuvant setting is one of the single most important therapeutic outcomes that can be obtained. Patients who achieve it have 7 to 10 years distant relapse-free survival rates over 90% compared to less than 50% for those who do not achieve a complete pathological response. The ISPY-2 Trial was developed in partnership with the FDA to try to accelerate the development of novel agents. It focuses on patients with stage II/III aggressive breast cancers and uses the neoadjuvant setting to identify drugs that shrink tumors rapidly. The trial represents a tremendously powerful “sandbox” to identify biomarkers to predict response to therapies and so far, several drugs have “graduated” from the trial and are being explored in phase III trials. Dr. Petricoin’s lab serves as the protein biomarker “engine” for the ISPY-2 trial. They will utilize their invention of the Reverse Phase Protein Array, which has gained great reputation for its unmatched ability to generate quantitative data for hundreds of important drug targets. Additionally, they have coupled this technology with Laser Capture Microdissection for the discovery of predictive biomarkers for a large number of ISPY-2 drugs. With previous support from Gateway, the investigators were able to identify subsets of patients that achieve very high rates of clinical responses to specific agents including neratinib, MK2206, and pembrolizumab. Now, new targeted agents require exploration including durvalumab, SD-101 with pembrolizumab, cemiplimab with REGN3767, dostarlimab with paclitaxel and carboplatin, dostarlimab with oliparib, and durvalumab with oliparib. This study will identify patients most likely to benefit from these agents. If the study is successful, it could lead to new and improved patient-specific treatments for breast cancer patients.
Trial Registration: ClinicalTrials.gov Identifier: NCT01042379
