Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations

Objective: To investigate the clinical features of patients with non-small cell lung cancer(NSCLC) harboring uncommon epidermal growth factor receptor(EGFR) mutations, and the treatment outcomes of EGFR tyrosine kinase inhibitors(TKIs) in these patients.Methods: We retrospectively analyzed the data of 128 NSCLC patients pathologically diagnosed with uncommon EGFR mutation in the Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and Beijing Hospital from January 2010 to December 2015, including 40 advanced patients who received EGFR-TKI.Results: Among the total 128 patients, 11 patients were non-adenocarcinoma, including squamous carcinoma(3.9%), adenosquamous carcinoma(2.3%), large cell carcinoma(0.8%), and composite neuroendocrine carcinoma(1.6%). Single mutations accounted for 75.0%(96/128), including G719X(29.7%), S768I(18.0%), 20 exon insertion(13.3%), L861Q(12.5%), De novo T790M(0.8%), and T725(0.8%). Thirty-two patients harbored complex mutations. Forty advanced patients received EGFR-TKI, the objective response rate(ORR) was 20.0%,the disease control rate(DCR) was 85.0%, and the progression-free survival(PFS) was 6.4 [95% confidence interval(95% CI), 4.8–7.9] months. The exploratory analysis of tumor response and PFS in 33 patients with G719X/S768I/L861 Q subtypes showed that ORR was 21.2%(7/33), the DCR was 93.9%(31/33), and PFS was 7.6(95% CI, 5.8–9.4) months. Patients with exon 20 insertion mutation and De novo T790 M experienced rapid disease progression with PFS no more than 2.7 months.Conclusions: Uncommon EGFR-mutant NSCLCs are heterogeneous, EGFR-TKIs can have different efficacy in this specific subtype, and thus further individual assessment is required for each case.