Benefit of second-line systemic chemotherapy for advanced biliary tract cancer: A propensity score analysis

Florian Moik,Renate Schaberl-Moser,Felix Prinz,Thomas Bauernhofer,Thomas Winder,Angelika Terbuch,Armin Gerger,Michael Stotz,Andreas Reicher,Joanna Szkandera,Jakob M Riedl,Florian Posch,Anne-Katrin Kasparek,Martin Pichler,Christopher H Rossmann,Herbert Stöger

doi:10.1038/s41598-019-42069-1

Abstract

Whether 2nd-line-chemotherapy (2LCTX) + best-supportive-care (BSC) benefits patients with advanced biliary tract cancer (aBTC) more than BSC alone is unclear. We therefore conducted a propensity-score-based comparative effectiveness analysis of overall survival (OS) outcomes in 80 patients with metastatic, recurrent, or inoperable aBTC, of whom 38 (48%) were treated with BSC + 2LCTX and 42 (52%) with BSC alone. After a median follow-up of 14.8 months and 49 deaths, the 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 (p = 0.0003; Hazard ratio (HR) = 0.36, 95%CI:0.20–0.64, p = 0.001). An inverse-probability-of-treatment-weighted (IPTW) analysis was conducted to rigorously account for the higher prevalence of favorable prognostic variables in the 2LCTX + BSC group. After IPTW-weighting, the favorable association between 2LCTX and OS prevailed (adjusted HR = 0.40, 95%CI: 0.17–0.95, p = 0.037). IPTW-weighted 6-, 12-, and 18-month OS estimates were 77%, 58% and 33% in the BSC + 2LCTX group, and 39%, 28% and 22% in the BSC group (p = 0.037). Moreover, the benefit of 2LCTX was consistent across several clinically-relevant subgroups. Within the limitations of an observational study, these findings support the concept that 2LCTX + BSC is associated with an OS benefit over BSC alone in aBTC.

Highlights

Whether 2nd-line-chemotherapy (2LCTX) + best-supportive-care (BSC) benefits patients with advanced biliary tract cancer more than BSC alone is unclear
A non-randomized comparison of these two treatment strategies has a high risk of bias, because patients receiving 2LCTX + BSC are likely selected on the basis of favorable oncologic and comorbidity profile, whereas patients assigned to BSC alone are likely to have poor performance status, comorbidities, obstructive bile duct pathology, or profoundly progressive disease rendering them ineligible for a further course of cytotoxic chemotherapy[11]
IPTW-weighing did not fully reduce imbalances below the pre-specified standardized mean difference (SMD) threshold of 0.20 for a small number of variables such as haemoglobin, we considered these balance diagnostics to be indicative of an adequate propensity score model

Summary

Introduction

Whether 2nd-line-chemotherapy (2LCTX) + best-supportive-care (BSC) benefits patients with advanced biliary tract cancer (aBTC) more than BSC alone is unclear. A non-randomized comparison of these two treatment strategies has a high risk of bias, because patients receiving 2LCTX + BSC are likely selected on the basis of favorable oncologic and comorbidity profile, whereas patients assigned to BSC alone are likely to have poor performance status, comorbidities, obstructive bile duct pathology, or profoundly progressive disease rendering them ineligible for a further course of cytotoxic chemotherapy[11]. This could lead to an overestimation of the “true” effect of 2LCTX in this setting. A propensity score analysis using inverse-probability-of-treatment-weights (IPTW) was implemented to rigorously account for non-random treatment assignment to 2LCTX

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