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Gewählte Publikation:

Moik, F.
Benefit of second-line systemic chemotherapy for advanced biliary tract cancer: A propensity score analysis
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2018. pp. [OPEN ACCESS]


Autor*innen der Med Uni Graz:
Gerger Armin
Posch Florian
Stotz Michael

Background Second-line-chemotherapy (2LCTX) is increasingly applied in patients with advanced-biliary-tract cancer (aBTC), although no randomized trial has so far demonstrated the benefit of this intervention over best-supportive-care (BSC) alone. In the absence of randomized data, we conducted a comparative effectiveness analysis of survival outcomes in aBTC patients treated with BSC±2LCTX. Methods This single-center observational cohort-study includes 80 patients (median age: 68 years, female: n=38 (48%), ECOG 1-2: n=27 (45%) with aBTC (metastatic, recurrent, or inoperable) who completed 1st-line-chemotherapy at the department of Oncology of the Medical University of Graz (overall: 185 BTC-patients 2003-2016)). Thirty-eight of these patients (48%) received 2LCTX in addition to BSC (Fluoropyrimidine-based-monochemotherapy: n=26 (68%), Fluoropyrimidine-based-polychemotherapy: n=8 (21%), other regimens: n=4 (11%)). Primary endpoint was 18-month-OS. An inverse-probability-of-treatment-weighted-analysis (IPTW) was conducted to rigorously account for imbalances in prognostic variables between the two groups. Results During a median follow-up of 14.8 months, we observed 49 deaths. Crude 6-, 12-, and 18-month Kaplan-Meier OS estimates were 77%, 53% and 23% in the BSC+2LCTX-group, and 29%, 21%, and 14% in patients in the BSC-group (log-rank p=0.0003; Hazard ratio (HR)=0.36, 95%CI:0.20-0.64, p=0.001). However, patients receiving 2LCTX+BSC had a significantly higher prevalence of favourable prognostic variables, such as a better ECOG-performance-status (p=0.05), metachronous metastasis (p=0.001), and lower C-reactive protein levels (p=0.04). These imbalances were strongly reduced by weighting of the data with the IPTW. In IPTW-adjusted analysis of time-to-death, the favourable association between 2LCTX and OS prevailed (Adjusted HR=0.42, 95% CI:0.18-0.96, p=0.04). In IPTW-weighted Kaplan-Meier analysis, 6-, 12-, and 18-month OS estimates were 74%, 57% and 33% in the BSC+2LCTX group, and 41%, 29% and 22% in patients in the BSC group (log-rank p=0.04). The favourable association of 2LCTX with OS slightly weakened over time (Schoenfeld test p=0.005). Otherwise, the observed benefit of 2LCTX was consistent across several subgroups, such as patients with and without objective response to 1st-line chemotherapy, as well as patients with and without moderate biliary stenosis (indicated by serum bilirubin levels). Conclusions: Within the limitations of an observational study, our data support the concept that 2LCTX+BSC is associated with an OS benefit over BSC alone in patients with aBTC.

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