Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data

Lorenzo Fornaro,Sara Lonardi,Giulia Pasquini,Michele Milella,Isabella Sperduti,Giovanni Brandi,Caterina Vivaldi,Chiara Caparello,Francesco Leone,Gianna Musettini,Giuseppe Aprile,Daniele Santini,Nicola Silvestris,Alfredo Falcone,Stefano Cereda,Enrico Vasile

doi:10.1186/s13046-015-0267-x

Abstract

BackgroundAfter progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far.MethodsWe collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings.ResultsA total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months).ConclusionsThe current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.

Highlights

After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers
Even in the absence of phase III data formally supporting the equivalence of different platinum salts in advanced biliary tract cancers (aBTC), oxaliplatin is widely considered a reasonable alternative to cisplatin: the combination of gemcitabine and oxaliplatin is often used in clinical practice as well as clinical trials as chemotherapy backbone for the evaluation of targeted agents [2]
Patients selection For the multicenter survey, we retrospectively identified patients with aBTC treated with second-line chemotherapy at 10 Italian Institutions between 2004 and 2013

Summary

Introduction

After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). In the majority of cases, disease occurs in an advanced stage and prognosis remains poor, with median overall survival (OS) times rarely exceeding the range 10–12 months [2]. In this setting, chemotherapy constitutes the mainstay of treatment strategy. Two randomized phase II and III studies have demonstrated significant survival advantage for the combination of gemcitabine and cisplatin over gemcitabine alone for patients with aBTC [6, 7]: gemcitabine plus cisplatin represents the current standard of care as first-line therapy. Several studies suggested that secondline treatment could be helpful for selected patients with good performance status, but no consensus has ever defined the most suitable regimen to use and the right patient to treat [8]

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