Second‐line chemotherapy in biliary tract cancer: Outcome and prognostic factors

Abstract

Background & Aims The prognosis of biliary tract cancer (BTC) is poor. Standard treatment for advanced BTC is a chemotherapy (CT) with gemcitabine and cisplatin. Phase III evidence for a second‐line (2L) CT is lacking. We aimed to investigate the feasibility of a 2L CT, to estimate the outcome and to identify prognostic markers. Methods Patients of our institution with advanced BTC between 2000 and 2015 receiving CT were included. Data were analysed in univariate and multivariate analysis. Results Three‐hundred and fifteen and 144 patients (45.7%) received first‐line (1L) and 2L CT respectively. The OS of patients receiving 2L CT was 16.67 and 9.9 months from the beginning of 1L and 2L CT respectively. The overall response rate and the disease control rate after 3 months were 9.7% and 33.6% respectively. Adverse events of grade 3 or more were observed in 26.1%. One patient died of gemcitabine‐related haemolytic uraemic syndrome. Age of more than 70 years was not associated with a poor outcome. In multivariate analysis, CEA levels of >3 µg/L (P = 0.004, hazard ratio [HR] 1.89, 95% CI 1.22, 2.91), cholinesterase (CHE) levels of <5 kU/L (P = 0.001, HR 2.11, 95% CI 1.34, 3.31) and leukocytosis (P = 0.001, HR 2.90, 95% CI 1.51, 5.56) were associated with poor survival. Conclusions Despite a relevant toxicity, our data suggest that 2L CT may be feasible in fit BTC patients. CEA elevation, leukocytosis and low CHE levels are unfavourable prognostic markers. Results from prospective randomized trials are urgently awaited.

New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma

“…When patients show cancer progression after first-line chemotherapy, a good PS ECOG is the most important selection factor for the activation of second-line therapy [30].…”

Current and novel therapeutic opportunities for systemic therapy in biliary cancer

“…Although the available data suggested that a subpopulation of patients, especially young patients and those with a good PS, could benefit from second-line chemotherapy, this benefit number seemed limited and the evidence was considered to be of insufficient quality (level C) to recommend secondline chemotherapy for aCCA as a standard of care strategy (24). One of the main challenges for the completion of adequately powered studies was the fact that, due to the aggressive behaviour of CCA, few patients (ranging from 10 to 40% in different series) are considered to be eligible for second-line treatment (22,(25)(26)(27)(28). In 2019, results from the ABC-06 clinical trial were reported (29).…”

Systemic therapy for advanced cholangiocarcinoma: new options on the horizon

“…Few studies have been conducted in patients with advanced CCA and progression after first-line therapy, so there is no established standard of care for these persons. There are also few data on selecting patients who might benefit from second-line therapy; the available studies consistently required good performance status to initiate second-line therapy [42][43][44][45] . Other prognostic factors are the treatment effect in first-line therapy (disease control or not), a low CA19-9 level, and the absence of peritoneal carcinomatosis [44,45] .…”