The efficacy of immune checkpoint inhibitors in biliary tract cancer with KRAS mutation

With a 15% incidence, KRAS is one of the most common mutations in biliary tract cancer (BTC) and is a poor prognostic factor. Immune checkpoint inhibitors (ICIs) as salvage therapy have modest activity in BTC.

There are limited data on the efficacy of ICIs according to KRAS mutation in BTC. We evaluated the efficacy of ICIs in BTC patients with or without KRAS mutations.

Retrospective observational study.

We conducted molecular profiling in BTC patients who received ICIs as salvage therapy. The expression of programmed death ligand 1 (PD-L1) on tumor cells was assessed using immunohistochemistry. The TruSight^TM Oncology 500 assay from Illumina was used as a cancer panel. We analyzed overall survival (OS) and progression-free survival (PFS) of ICI in BTC patients according to KRAS mutation and PD-L1 expression.

A total of 62 patients were included in this analysis. The median age was 68.0 years; 47 patients (75.8%) received pembrolizumab and 15 (24.2%) received nivolumab as salvage therapy. All patients received gemcitabine plus cisplatin as the frontline therapy, and 53.2% received fluoropyrimidine plus oxaliplatin (FOLFOX) before ICI. The median number of lines of prior chemotherapy was 2.5. The KRAS mutation was found in 13 patients (19.1%), and 28 patients (45.2%) showed 1% or more of tumor cells out of visible tumor cells positive for PD-L1. There was no statistical correlation between KRAS mutation and PD-L1 expression. The median OS and PFS with ICI were 5.6 [interquartile range (IQR): 3.3-8.0] and 3.8 (IQR: 3.0-4.5) months, respectively. There were no statistically significant differences in PFS with ICIs according to KRAS mutation (mutant type versus wild type) and PD-L1 expression (positive versus negative). In subgroup analysis, patients with both KRAS mutation and PD-L1 positivity had longer PFS compared with patients with KRAS mutation and PD-L1 negativity (10.1 versus 2.6 months, p = 0.047). This finding was not shown in patients with wild-type KRAS.

Our analysis suggested that PD-L1 expression might be a useful biomarker for ICIs in BTC patients with KRAS mutation but not in those with wild-type KRAS.