Abstract
BackgroundUncommon epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a rare subset of NSCLC. The aim of this study was to investigate the prevalence, characteristics, and clinical outcomes of metastatic NSCLC harboring uncommon EGFR mutation at Thailand’s largest national tertiary hospital. The secondary objective was to compare treatment efficacy between EGFR-tyrosine kinase inhibitor (EGFR-TKI) and chemotherapy.MethodsThis retrospective chart review included patients that were tested for EGFR-mutation NSCLC during 2014–2018. Patient demographic and clinical data, treatment data, and outcome data were collected and analyzed.ResultsOf the 681 patients that were evaluated for EGFR mutation, 317 (47.0%) had EGFR-mutant NSCLC, and 28 (8.8%) of those harbored uncommon EGFR mutations. The median follow-up was 19.1 months. History of tobacco use was reported in 50% of patients. The most common single mutation among uncommon EGFR was exon 20 insertion (n = 6), followed by L861Q (n = 5) and G719X (n = 4). Thirteen (46%) patients had compound mutations. One hundred percent of male patients with G719X mutation were smokers. Sixteen of 28 patients were treated with EGFR-TKI. Most received first-generation EGFR-TKI, and 29% were treated with chemotherapy alone. The objective response rate was 37.5% in the EGFR-TKI group. Median progression-free survival (PFS) in the EGFR-TKI group was 10.2 months. Median PFS among the 8 patients in the chemotherapy group that received first-line platinum doublet was 6.5 months. Three-year overall survival (OS) among 28 patients was 34%. Three-year OS was significantly better in patients treated with EGFR-TKI.ConclusionsUncommon EGFR mutations was detected in 8.8% of EGFR-mutant NSCLC. Exon 20 insertion was the most common mutation, and 50% of patients had history of tobacco use. First- or second-generation EGFR-TKI demonstrated greater OS benefit than platinum-doublet chemotherapy among patients harboring uncommon EGFR-mutant NSCLC. Survival outcomes were comparable to those reported from previous large cohort studies.
Highlights
Uncommon epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a rare subset of NSCLC
Baseline characteristics Of the 681 patients that were evaluated for EGFR mutation, 317 (47.0%) had EGFR-mutant NSCLC, and 28 (8.8%) of those harbored uncommon EGFR mutations
ECOG 0–1 was equal between tyrosine kinase inhibitor (TKI) and chemotherapy group (15 of 16 and 7 of 8, respectively). 64% presented with extra-pulmonary metastasis, and 17% had a CNS metastasis
Summary
Uncommon epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a rare subset of NSCLC. Standard systemic treatment for patients with stage IIB/IV NSCLC with sensitizing epidermal growth factor receptor (EGFR) mutation includes either first-generation EGFR-tyrosine kinase inhibitor (TKI) (gefitinib or erlotinib) or second-generation TKI (afatinib). Previous phase III studies reported a response rate by first- or second-generation EGFR-TKI of 50–60%, with significantly longer progression-free survival (PFS) than platinum-doublet chemotherapy (CMT) [4,5,6,7,8,9]. The most recent data from combined post-hoc analysis of the LUX-Lung 2, 3, and 6 trials revealed lower median overall survival (OS) in patients treated with afatinib (19.4 months) compared to those treated with platinum-doublet CMT (30.2 months) among patients with uncommon or complex mutation [12]
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