Efficacy of targeted therapy in patients with non-small cell lung cancer harboring very rare mutations in EGFR exon 18

Abstract

Background: Somatic mutations in epidermal growth factor receptor (EGFR) exon 18 are classified as uncommon or rare mutations in non-small cell lung cancer (NSCLC), in this context, other than G719X or E709X exon 18 mutations are even more rare and heterogeneous. In such scenario, first line treatment options are still debated. The aim of this study was to investigate the response of NSCLC patients harboring very rare exon 18 mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs).

Methods: This retrospective descriptive study included 105 patients with NSCLC harboring mutations in EGFR exon 18 diagnosed at West China Hospital. The clinical response to EGFR-TKIs was evaluated according to different classifications of mutations in 45 NSCLC patients: 39 harboring G719X or E709X mutations and 6 harboring very rare mutations in EGFR exon 18.

Results: Among 105 patients, 84% (88/105) harbored rare mutations in EGFR exon 18, including G719X and E709X mutations. The remaining 16% (17/105) had very rare mutations in EGFR exon 18, including E709_710delinsX and G724S. For the subsequent efficacy analysis of EGFR-TKI in 45 NSCLC patients, patients harboring very rare mutations achieved a favorable disease control rate (DCR) of 100% and had a median progression-free survival (PFS) of 17.2 months, which was not significantly different compared to patients harboring G719X or E709X (P=0.59).

Conclusions: EGFR-TKIs showed great efficacy in terms of responses and survival in patients harboring exon 18 EGFR rare mutations. This may justify the use of targeted therapies as a potential treatment strategy for these patients.

Keywords: Non-small cell lung cancer (NSCLC); efficacy; epidermal growth factor receptor (EGFR); targeted therapy; very rare mutations.

Figure 1

Distribution of different EGFR mutations in exon 18 in 105 NSCLC patients. EGFR mutations were subdivided into G719X or E709X group (88/105, 84%) and very rare mutation group (17/105, 16%) (left). Very rare mutations in EGFR exon 18 included E709_710delinsX, G724S, L707F, V689L/M, L718V/Q, K714N, and S720F (right). NSCLC, non-small cell lung cancer.

Figure 2

Clinical response in patients harboring G719X or E709X and those harboring very rare mutations in EGFR exon 18. (A) A waterfall plot showing the tumor retraction ratio of patients who received EGFR-TKIs; (B) histogram showing the proportions of patients with controlled disease with G719X or E709X and very rare mutations. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor.

Figure 3

Duration of survival status to EGFR-TKIs. A swimming chart showing the survival status of patients with G719X or E709X mutations and very rare mutations. EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; OS, overall survival; PFS, progression-free survival.

Figure 4

Clinical outcome in the different types of mutations in EGFR exon 18. (A) Kaplan-Meier curve of PFS of EGFR-TKI treatment in 45 NSCLC patients with G719X or E709X mutations in EGFR exon 18 and very rare mutations in EGFR exon 18; (B) Kaplan-Meier curve of OS of EGFR-TKI treatment in 45 NSCLC patients with G719X or E709X mutations in EGFR exon 18 and very rare mutations in EGFR exon 18. EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; PFS, progression-free survival; CI, confidence interval; OS, overall survival; NR, not reached; NSCLC, non-small cell lung cancer.