Efficacy of ICIs on patients with oncogene-driven non-small cell lung cancer:a retrospective study

Aim:The objective of our study was to assess the efficacy of immune checkpoint inhibitors(ICIs)on patients with non-small-cell lung cancer(NSCLC)harboring oncogenic alterations.Methods:We retrospectively enrolled patients with advanced non-squamous NSCLC who were treated with anti-PD-1-based monotherapy or combined immunotherapy.Major characteristics including PD-L1 expression,treatment,and survival were analyzed.Results:In total,309 non-squamous NSCLC patients with a median age of 61 years(range 20-88 years)including 70.9%male were retrospectively enrolled.The molecular alterations involved epidermal growth factor receptor(EGFR)(n=81),V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)(n=31),anaplastic lymphoma kinase(ALK)(n=1),human epidermal growth factor receptor 2(HER2)(n=12),V-raf murine sarcoma viral oncogene homolog(BRAF)(n=2),rearranged during transfection(n=4),and c-ros oncogene 1(ROS1)(n=3).In the EGFR subset,the ORR was 30.9%(n=81)and PFS was significantly shorter than WT group(median PFS:5.7 months vs.7.1 months;P=0.0061).In subgroup analyses,ICI combined therapy was significantly correlated with a longer PFS compared with ICI monotherapy(median PFS:7.7 months vs.4.7 months;P=0.0112).In KRAS patients,ORR was 51.6%(n=31).No significant difference was found in subgroup analyses.The ORR and PFS were 16.7%(n=12)and 28.6%(n=7),7.8 months and 9.0 months for HER2 and EGFR Exon20 insertion patients,respectively.Three ROS1 patients were enrolled with a PFS of 16.0,34.2,and 45.0 months individually,and one ALK patient with PFS of 4.4 months was identified.No response was found in two BRAF patients.Conclusion:ICI-based combination therapy can bring benefit to patients with EGFR-mutant NSCLC.ICI-based combination therapy could be considered for patients with ROS1 rearrangement,HER2 mutation and EGFR Exon20 insertion NSCLC.