Trastuzumab beyond progression for HER2 positive metastatic breast cancer: progression-free survival on first-line therapy predicts overall survival impact.

Trastuzumab beyond first progression in the metastatic setting has been adopted based on limited data suggesting improved outcomes compared to second-line chemotherapy alone although predictive factors for preferential benefit remain elusive. We conducted a retrospective review of all patients receiving trastuzumab for HER2 + metastatic disease between Jan 1, 1999-June 15, 2011. Univariate and time to event analyses described treatment and survival patterns. Median duration of each line of therapy and overall survival times for covariates, including treatment era (pre versus post Jan 1, 2005), lines of trastuzumab-based therapy (1 versus 2 versus 3 + ), first-line chemotherapy partner (docetaxel/paclitaxel versus other) and median exposure to first-line trastuzumab-based therapy (=/> versus < cohort median) were estimated. A total of 119 patients received a median of two lines of trastuzumab-based therapy (range 1-8). Median overall survival was 21.8 months (95% CI = 14.5-27.1 m), by era was 15.6 m (95% CI = 9.7-24.8 m) versus 26.1 m (95% CI = 20.0-39.3 m; p = 0.11) and by lines of trastuzumab-based therapy received was 10.6 m (95% CI = 5.3-17.4 m) versus 13.9 m (95% CI = 9.5-27.6 m) versus 32.5 m (95% CI = 25-49.4 m) (p = 0.0014). Median overall survival was significantly longer for those receiving taxanes with trastuzumab compared to other first line partners (26.1 m, 95% CI = 17.8-31.4 m versus 14.5 m, 95% CI = 9.4-21.9 m, p = 0.02). Median overall survival with duration of first-line trastuzumab-based therapy =/> cohort median was 31.9 m (95% CI = 26.2-52.2 m) versus 10.3 m for shorter durations (95% CI = 6.9-15.6 m; p < 0.0001). Our observations support progression-free survival on first-line trastuzumab-based therapy as a clinically relevant predictive factor for overall survival benefit with the adoption of a trastuzumab beyond progression treatment strategy.

Adjuvant chemotherapy for breast cancer: a cost-utility analysis of FEC-D vs. FEC 100.

BACKGROUND: Adjuvant 5-flurouracil, epirubicin and cyclophosphamide-docetaxel (FEC-D) has been shown to improve disease-free and overall survival (DFS and OS), compared to FEC 100, for node-positive breast cancer. An economic evaluation was undertaken to examine the cost-utility (CU) of FEC-D relative to FEC 100 given possible differences in cost between the two regimens. METHODS: A Markov model was developed to calculate the cumulative costs and quality-adjusted life years (QALY) gained over a 10-year horizon for a hypothetical cohort of 1,000 women with node-positive breast cancer treated with FEC 100 or FEC-D. Event rates, costs, and utilities were derived from the literature. Efficacy outcomes were based primarily on the hazard ratio of DFS for all patients, but separate analyses were also conducted according to age and menopausal status as per the PACS 01 subgroup analysis results. The model took a third-party direct payer perspective and reports results in 2006 Canadian dollars ($). Both costs and benefits were discounted at 3%. RESULTS: FEC-D is associated with 0.156 QALY gain and a $2,280 incremental cost compared to FEC 100, with a CU of $14,612/QALY gained. Results were robust to model assumptions and input parameters in a sensitivity analysis but were marginal in pre-menopausal and younger women. CONCLUSIONS: Adjuvant FEC-D is a cost-effective alternative to FEC 100, with a cost-effectiveness ratio well below commonly employed thresholds. The CU according to age and menopausal status should be considered in view of the potential differences in efficacy in these subgroups, if any.