KRAS mutation + PD-L1 expression

Patients completing two-years of pembrolizumab for NSCLC in an Australian cohort had high rates of KRAS mutation and PD-L1 expression; a proportion had brain metastases and treated oligoprogression. Progression post pembrolizumab was higher in PD-L1 TPS < 1% and in those without complete response.

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...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.

PEAC is a disease of genetic heterogeneity. The administration of EGFR and ALK inhibitors was effective in patients with PEAC. PD-L1 expression and KRAS mutation type may be used as predictive biomarkers for immunotherapy in PEAC. This study provided both theoretical basis and clinical evidence for PEAC.

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% had fluoropyrimidine plus oxaliplatin (FOLFOX) before ICIs...In subgroup analysis, patients with both KRAS mutation and PD-L1 positivity had longer PFS as compared to patients with KRAS mutation and PD-L1 negativity (6.5 vs 2.6 months, p=0.047). This finding was not shown in patients with a wild type of KRAS.ConclusionThis analysis showed that PD-L1 expression might be a novel biomarker for ICIs in BTC patients with KRAS mutation but not the wild type of KRAS.

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% had fluoropyrimidine plus oxaliplatin (FOLFOX) before ICIs... The PD-L1 expression might be a novel biomarker for ICIs in BTC patients with KRAS mutation but not in those with the wild type of KRAS.

Our results suggest that ERK signaling inhibition contributes to the reduction of PD-L1 expression through the autophagy pathway in iCCA. As a supplement to anti-PD-1/PD-L1 immunotherapy, ERK-targeted therapy may serve as a potentially novel treatment strategy for human KRAS-mutated iCCA.