Abstract 12035: Cardiotoxicity-Based Model for Assessment of Drug Value in Breast Cancer

Abstract

Introduction: Cardiovascular toxicity mediated by chemotherapy drugs has important implications on the clinical outcomes of patients with breast cancer. We created a multi-component drug value framework incorporating efficacy, safety, cost, and cardiovascular toxicity data to define the overall value of standard regimens. The impact of heart failure incidence on the value score of each regimen was evaluated. Methods: The NCCN guidelines were reviewed, and four standard chemotherapy regimens used in non-metastatic HER-2 negative breast cancer were selected. PubMed was reviewed for randomized clinical trials establishing the role of each regimen. Data on the efficacy (defined as 5-year survival) and toxicity (defined as incidence of the most frequent grade 3 toxicity) profile of each regimen were extracted. Data on regimen-specific heart failure incidence at follow up were collected from prospective studies. Regimen-specific costs were derived from a recent observational cohort study. Total drug value scores (range 2.2-8.6, traditional, 2.9-11.7 upgraded) were computed and the effect of cardiotoxicity data on drug value scores was evaluated. Results: Anthracycline-containing regimens had lower mean drug value scores than anthracycline-free regimens (5.3, 61.6% versus 7.4, 86.0%) using a traditional value system based on efficacy, safety, and cost. When data on heart failure incidence were incorporated into the value assessment, anthracycline-containing regimens had lower relative value scores (mean decrease 10.7%) while anthracycline-free combinations had higher relative scores (mean increase 4.3%), compared with a traditional model. Regimen-specific value scores were modified by the addition of heart failure data. Drug value assessments that included efficacy, safety and cost showed superiority of docetaxel, adriamycin, cyclophosphamide (TAC) relative to cyclophosphamide, methotrexate, fluorouracil (CMF) (7.1, 82.6%, 6.6, 76.7%) and the addition of heart failure incidence data reversed that trend (8.6, 73.5%, 9.6, 82.0%). Conclusions: Inclusion of cardiovascular toxicity data modifies the value scores of standard chemotherapy regimens used in breast cancer and likely provides a more patient-centric value assessment.