Uncommon EGFR mutations in lung carcinoma: features and treatment outcomes in a retrospective French cohort

Background: The best management for rare epidermal growth factor receptor (EGFR) mutations in advanced non-small cell lung carcinoma (NSCLC) remains uncertain. The literature indicates that response to usual treatment could differ in certain subgroups such as exon 20 insertion/duplication (E20ID), other single uncommon mutation (OSUM), and EGFR complex mutation (ECM). Methods: In this observational, regional, multi-center, retrospective study, we gathered data on uncommon EGFR mutations in NSCLC from 2007 to 2021. We analyzed patient characteristics, prognostic factors and treatment outcomes [objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS)]. Results: Among 119 patients with an uncommon EGFR mutant, 34 harbored E20ID, 23 ECM, and 62 OSUM. There were significantly more non-smokers in E20ID. Female gender and performance status <2 were associated with a better prognosis. Among the 97 metastatic patients with available data for 1st line treatment, median estimated OS was 21 months (95% CI: 18???31), with better non-significant OS for ECM. Median estimated PFS was 7 months (95% CI: 4???9). We found significant differences in ORR, DCR and PFS favoring 1st line chemotherapy for E20ID, whereas the outcomes for OSUM and ECM were more favorable for tyrosine kinase inhibitor (TKI) (mainly 2nd and 3rd generation). Conclusions: There were variations in treatment outcomes among subgroups in our cohort. Exon 20 insertions showed better ORR and PFS with 1st line chemotherapy compared to TKI. Conversely, other rare EGFR mutations including ECM had better ORR and PFS with TKI than chemotherapy. There was no significant difference in OS among treatment groups overall or within rare mutation subgroups.