ICIs as Salvage Therapy for BTCs with KRAS Mutation

KRAS is one of the most common oncogenes among all cancer types. Activation of the KRAS pathway results in cell proliferation, differentiation, and migration and inhibition of apoptosis, leading to oncogenesis, immune escape, and evasion. These actions suggest a possible synergistic effect with immunotherapy. Despite having an incidence of approximately 15% in biliary tract cancer (BTC), treatment of patients with KRAS mutations in BTC has had modest efficacy, specifically with immune checkpoint inhibitors (ICIs) as salvage therapy. Dr Sun Young Jeong presented results from a retrospective analysis of molecular profiles in patients with BTCs to assess the efficacy of ICIs according to KRAS mutation.

Eligible patients had BTC and received ICI salvage therapy between March 2020 and August 2022. PD-L1 expression was considered positive if observed in ≥1% of tumor cells. Efficacy end points included progression-free survival (PFS) and overall survival according to PD-L1 expression and KRAS mutation. Tumor mutational burden, PD-L1 expression, and tumor-infiltrating lymphocytes were also assessed.

A total of 62 patients with BTC were included in the analysis. Of these, 13 (19.1%) patients harbored KRAS mutations, whereas 28 (45.2%) patients were PD-L1 positive. No statistical correlation was found between KRAS mutation and PD-L1 positivity (P = .589). Of the 62 patients studied, 47 received salvage pembrolizumab, and 15 patients received salvage nivolumab. All patients received gemcitabine/cisplatin as first-line therapy, and 53.2% of patients also received FOLFOX before ICI salvage. Patients who had a KRAS mutation and were PD-L1 positive (n = 6) had a longer PFS than those who were PD-L1 negative with a KRAS mutation (n = 7): 10.1 months versus 2.8 months (P = .047). No statistically significant difference was found regarding PFS between PD-L1–negative and PD-L1–positive patients who were KRAS wild type: 4.6 months versus 3.3 months (P = .472).

In general, the presence of a KRAS mutation and PD-L1 expression did not predict efficacy of ICI salvage therapy in patients with BTC. PD-L1 expression may be a biomarker of ICI use in patients with KRAS mutations; however, this does not apply to patients with KRAS wild-type mutations.

Source: Jeong SY, Jang JY, Hong JY, et al. The efficacy of immune checkpoint inhibitors in biliary tract cancer with KRAS mutations. Poster presented at: ASCO Gastrointestinal Cancers Symposium, January 19-21, 2023; San Francisco, CA. Abstract 598.