First Line and Second Line Chemotherapy in Advanced Cholangiocarcinoma and Impact of Dose Reduction of Chemotherapy: A Retrospective Analysis

Abstract

ObjectivePrognosis of patients with irresectable cholangiocarcinoma is still poor. The ABC-02 trial established the current first line (1L) standard systemic chemotherapy (CT) with gemcitabine/platinum derivate for advanced cholangiocarcinoma. However, the majority of patients needed therapy adaptions. Thus, the aim of this study was to evaluate 1L and second line (2L) therapy regimens and the impact of therapy adaptions in an unselected real-life cohort of patients with advanced cholangiocarcinoma.Materials and MethodsThis is a single institution retrospective analysis of patients with irresectable cholangiocarcinoma who were treated with gemcitabine/platinum derivate from 2010 to 2018. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed for all patients, especially with regard to CT de-escalation.ResultsFifty-eight patients receiving gemcitabine/platinum derivate were included in the analysis. Median OS and PFS were 12.2 and 6.9 months. Interestingly, 41 patients (71%) needed therapy de-escalation. However, despite reduced CT exposition, there was no-significant difference in OS (10.8 months vs. 15.6 months, p = 0.127), and patients suffered from less adverse events during CT. 21 (36%) patients reached 2L CT, most often with FOLFIRI (57%). Survival beyond the end of 1L CT was 7.1 months with 2L CT vs. 2.9 months with BSC.ConclusionIn our study, the combination of gemcitabine/platinum derivate showed similar OS and PFS as randomized prospective phase II/III trials. Therapy regimen adaptions were needed in the majority of patients. However, individualized modifications of the therapy regimen allowed better tolerance as well as continuation of therapy and did not significantly influence median OS. Furthermore, our study revealed a potential survival benefit with 2L CT for selected patients.

Comparison between regular additional endobiliary radiofrequency ablation and photodynamic therapy in patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy

“…Nevertheless, it must to be highlighted that the baseline characteristics onset of any cancer-specific therapy were similar between the three treatment groups. However, the triple-therapy group received significantly more often a second-line SC and that could positively affect the OS (14,42,43). Potentially, the trend to a longer OS within the triple group might be an indication for summation potential of the beneficial effects of concomitant ePDT and eRFA.…”

“…The recently published TOPAZ-1 trial demonstrated the beneficial effect of adding durvalumab to gemcitabine and cisplatin ( 13 ). Under gemcitabine and cisplatin, patients showed a median overall survival (OS) between 11.1 and 12.2 months ( 14 ). The addition of durvalumab to the established regimen improved OS to 12.8 months ( 13 ).…”

Case Report: Sustained complete remission on combination therapy with olaparib and pembrolizumab in BRCA2-mutated and PD-L1-positive metastatic cholangiocarcinoma after platinum derivate

“…When curative resection is not possible, palliative systemic chemotherapy remains as standard therapy. To date, most regimes introduce a gemcitabine- and platinum-based therapy as first line, based on the results of the ABC-02 study ( 20 ), followed by a 5-FU doublet combination as second-line (ABC-06) ( 21 , 24 ). In recent years, tumor sequencing as part of the concept of personalized tumor therapy has emerged as a crucial tool.…”

Ex vivo liver resection and auto-transplantation and special systemic therapy in perihilar cholangiocarcinoma treatment

“…Nevertheless, this regimen could increase resectability only in few patients. In addition, most of patients required dose adaptions[ 28 ]. That forced researchers to seek other systemic agents including targeted therapy to increase survival and as a bridge to curative surgery in advanced disease.…”