Lead Investigator: Joshua Drago, Memorial Sloan Kettering Cancer Center
Title of Proposal Research: Statin use and clinical outcomes on ado-trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer
Vivli Data Request: 7535
Funding Source: None
Potential Conflicts of Interest: Honoraria: OncLive
Advisory Board: Biotheranostics
Funded Research: AstraZeneca
These declared conflicts are not relevant to the proposed project but will nonetheless be declared on any future publications of these data.
Summary of the Proposed Research:
Membrane epidermal growth factor receptor 2 (HER2) expression levels strongly influence the activity of therapies that target HER2 in cancers, including breast cancer. A protein called caveolin-1 (CAV-1) regulates the amount of HER2 expressed on cancer cells, and this expression can be modulated with cholesterol-depleting drugs, such as statins. In cell models, statins can increase the effectiveness of HER2-targeted therapies. One such therapy is ado-trastuzumab emtansine (T-DM1), which is commonly used in metastatic breast cancer that over-expresses HER2. We have initial evidence from a small sample size that taking patients who take statins along with T-DM1 have better cancer-related outcomes. We hope to confirm these findings using a larger sample size from the KAMILLA trial, in which over 2000 patients with metastatic HER2-positive breast cancer were treated with T-DM1. If we observe the same relationship, that will support the conduct of a prospective clinical trial combining statins with HER2-targeted therapies in breast cancer.
Statistical Analysis Plan:
This study was chosen because it represents a large, prospective trial in the population of interest (i.e. membrane epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) being treated with ado-trastuzumab emtansine (T-DM1)) which is expected to have complete data on all relevant variables of interest. For the primary analysis, patients who are and are not taking concurrent statins would be compared on the basis of overall response rate (ORR) and progression-free survival (PFS), both in unadjusted and adjusted analyses (accounting for relevant clinical covariates that may act as confounders, such as age, treatment line, hormone receptor status, and pre-treatment HER2 expression levels with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) if available). In exploratory analyses, toxicity patterns can be compared between these two patient cohorts, including hematologic, neurologic, and cardiac toxicity. Patients with missing data will be excluded. If observed, confirmatory data in a large cohort supporting the link between statin use and T-DM1 efficacy could justify the design of prospective clinical trials investigating combination therapy in HER2+ MBC.
Requested Studies:
A Two-Cohort, Open-Label, Multicenter Study of Trastuzumab Emtansine (T-DM1) in HER2-Positive Locally Advanced or Metastatic Breast Cancer Patients Who Have Received Prior Anti-HER2 and Chemotherapy-Based Treatment
Data Contributor: Roche
Study ID: NCT01702571
Sponsor ID: MO28231
Summary of Results:
We were unable to bring our analysis to completion due to paucity of the population of interest in the dataset. Although we did not complete our SAP, key learnings were that (within the limitations of this analysis), statin use was not associated with progression free survival in this study population.