George Dranitsaris1, Stefan Gluck2, Claudio Faria3, David Cox3, Hope Rugo4. 1. Augmentium Pharma Consulting Inc, Toronto, Ontario, Canada. Electronic address: george@augmentium.com. 2. Sylvester Comprehensive Care Center, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida. 3. Eisai Inc, Woodcliff Lake, New Jersey. 4. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
Abstract
PURPOSE: There has been considerable progress in the treatment of metastatic breast cancer. However, the identification of optimal cytotoxic agents in patients with triple-negative breast cancer (TNBC) (negative for hormone receptors and human epidermal growth factor receptor 2) remains a therapeutic challenge. We conducted a comparative effectiveness analysis of 4 cytotoxic agents in patients with TNBC. METHODS: We retrospectively identified patients who received single-agent chemotherapy with eribulin, capecitabine, gemcitabine, or vinorelbine from 19 community oncology clinics across the United States. Data collection included baseline patient and disease characteristics, prior therapies, performance status, duration of current therapy, growth-factor use and other supportive care, and dose-limiting toxicities and associated dose reductions or delays or skipped doses. Time to treatment failure (TTF) was measured from the first cycle of chemotherapy until disease progression, discontinuation due to toxicity, or death. TTF was estimated using the Kaplan-Meier method and Cox proportional hazards modeling adjusted for clustering on the practice site. To control for selection bias, which is inherent in observational studies, a propensity score-weighted TTF analysis was also conducted. FINDINGS: Data from 225 patients were included in the analysis (eribulin, 47 patients; capecitabine, 69; gemcitabine, 56; and vinorelbine, 53). The median age of each group was <60 years, with the exception of the gemcitabine group (63 years). The 4 groups were comparable with respect to age, performance status, duration of disease-free survival, presence of comorbidities, and hemoglobin level before the start of chemotherapy. Median lines of therapy of eribulin, capecitabine, gemcitabine, and vinorelbine and were 4th, 2nd, 3rd, and 3rd, respectively. The median durations of treatment were ~2 months with eribulin, capecitabine, and gemcitabine compared with 1.6 months with vinorelbine. Using eribulin as the reference drug, and with adjustment for line of therapy and associated prognostic factors, the propensity score-weighted Cox regression analysis did not identify significant between-treatment differences in TTF (hazard ratios [95% CI] vs eribulin: capecitabine, 1.15 [0.75-1.76]; gemcitabine, 0.62 [0.34-1.13]; and vinorelbine, 1.0 [0.67-1.67]). IMPLICATIONS: In this assessment of patients with TNBC treated in a community oncology setting, eribulin was utilized in later lines compared with the other agents. However, comparable drug activity was reported among the 4 agents.
PURPOSE: There has been considerable progress in the treatment of metastatic breast cancer. However, the identification of optimal cytotoxic agents in patients with triple-negative breast cancer (TNBC) (negative for hormone receptors and human epidermal growth factor receptor 2) remains a therapeutic challenge. We conducted a comparative effectiveness analysis of 4 cytotoxic agents in patients with TNBC. METHODS: We retrospectively identified patients who received single-agent chemotherapy with eribulin, capecitabine, gemcitabine, or vinorelbine from 19 community oncology clinics across the United States. Data collection included baseline patient and disease characteristics, prior therapies, performance status, duration of current therapy, growth-factor use and other supportive care, and dose-limiting toxicities and associated dose reductions or delays or skipped doses. Time to treatment failure (TTF) was measured from the first cycle of chemotherapy until disease progression, discontinuation due to toxicity, or death. TTF was estimated using the Kaplan-Meier method and Cox proportional hazards modeling adjusted for clustering on the practice site. To control for selection bias, which is inherent in observational studies, a propensity score-weighted TTF analysis was also conducted. FINDINGS: Data from 225 patients were included in the analysis (eribulin, 47 patients; capecitabine, 69; gemcitabine, 56; and vinorelbine, 53). The median age of each group was <60 years, with the exception of the gemcitabine group (63 years). The 4 groups were comparable with respect to age, performance status, duration of disease-free survival, presence of comorbidities, and hemoglobin level before the start of chemotherapy. Median lines of therapy of eribulin, capecitabine, gemcitabine, and vinorelbine and were 4th, 2nd, 3rd, and 3rd, respectively. The median durations of treatment were ~2 months with eribulin, capecitabine, and gemcitabine compared with 1.6 months with vinorelbine. Using eribulin as the reference drug, and with adjustment for line of therapy and associated prognostic factors, the propensity score-weighted Cox regression analysis did not identify significant between-treatment differences in TTF (hazard ratios [95% CI] vs eribulin: capecitabine, 1.15 [0.75-1.76]; gemcitabine, 0.62 [0.34-1.13]; and vinorelbine, 1.0 [0.67-1.67]). IMPLICATIONS: In this assessment of patients with TNBC treated in a community oncology setting, eribulin was utilized in later lines compared with the other agents. However, comparable drug activity was reported among the 4 agents.
Authors: Jennifer R Diamond; S G Eckhardt; Todd M Pitts; Adrie van Bokhoven; Dara Aisner; Daniel L Gustafson; Anna Capasso; Sharon Sams; Peter Kabos; Kathryn Zolman; Tiffany Colvin; Anthony D Elias; Anna M Storniolo; Bryan P Schneider; Dexiang Gao; John J Tentler; Virginia F Borges; Kathy D Miller Journal: Breast Cancer Res Date: 2018-08-02 Impact factor: 6.466