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.

A 3-week gemcitabine-cisplatin regimen for metastatic urothelial cancer.

OBJECTIVE: To assess the efficacy and tolerability of a 3-week outpatient schedule of intravenous gemcitabine and cisplatin in patients with locally advanced unresectable or metastatic transitional cell carcinoma of the urothelial tract (TCC). PATIENTS AND METHODS: A two-stage phase II trial enrolled TCC patients with Karnofsky performance status > or = 60, measurable disease, and adequate organ function. Prior adjunctive chemotherapy was allowed provided it had been completed at least 1 year prior to study entry. Treatment consisted of gemcitabine 1250 mg/m2 iv days 1 and 8 plus cisplatin 70 mg/m2 day 1 iv repeated every 21 days. The primary outcome was the objective response rate. RESULTS: Thirty patients were enrolled at six Canadian centres. Three complete and 10 partial responses were observed in 29 eligible patients (overall response rate 45% [95%CI, 27-63%]). Three patients had stable disease and 13 had progressive disease. The relative dose-intensities of gemcitabine and cisplatin were 81% and 88%, respectively. Toxicity was primarily hematological, and 60% of patients experienced at least one episode of grade 3 or 4 toxicity. One patient died of neutropenic sepsis and two died of vascular events while on treatment. CONCLUSIONS: The efficacy and tolerability of this schedule are similar to that reported with the standard 4-week schedule of gemcitabine-cisplatin. In the absence of a large randomized trial, the similarity of these results supports the use of this 3-week program in typical TCC patients treated in both community and academic cancer clinic settings.