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. 2019 Jun 17;19(1):595.
doi: 10.1186/s12885-019-5820-0.

EGFR exon 20 insertion mutations and response to osimertinib in non-small-cell lung cancer

Wenfeng Fang  1 , Yihua Huang  2 , Shaodong Hong  2 , Zhonghan Zhang  2 , Minghui Wang  3 , Jiadi Gan  2 , Wenjing Wang  4 , Honglin Guo  4 , Kai Wang  4 , Li Zhang  5
Affiliations

EGFR exon 20 insertion mutations and response to osimertinib in non-small-cell lung cancer

Wenfeng Fang et al. BMC Cancer. .

Abstract

Background: Epidermal growth factor receptor exon 20 insertion (EGFRex20ins) mutations represent approximately 4-12% of EGFR mutations and are generally refractory to the 1st and 2nd generation EGFR tyrosine kinase inhibitors (TKIs). Development of effective therapies for patients with EGFRex20ins mutant non-small-cell lung carcinoma (NSCLC) represents a great unmet need. Preclinical models have shown that osimertinib is active in NSCLC harboring EGFRex20ins, while the antitumor activity of osimertinib remains to be evaluated in patients with EGFRex20ins mutations.

Methods: Tumor genotyping was performed in 2316 Chinese NSCLC cases with targeted next generation sequencing (NGS) covering the whole exons of EGFR gene. The frequency and genetic characteristics of EGFRexon20ins mutations were analyzed. Furthermore, six patients with specific EGFRexon20ins mutations and receiving osimertinib 80 mg once daily were retrospectively included to assess the antitumor activity and safety of monotherapy osimertinib.

Results: EGFRex20ins mutations were identified in 4.8% (53/1095) of EGFR mutant NSCLC and 2.3% (53/2316) of all NSCLC cases. The most frequently identified EGFRexon20ins is A767_V769dup (17/53,32.1%). We found that the genetic characteristics of EGFRex20ins mutations in Chinese patients with NSCLC were comparable to those reported in Caucasian patients. Four patients with osimertinib therapy achieved partial response and the rest stable disease. Median progression free survival (PFS) was 6.2 months (95% confidence interval 5.0-12.9 months; range 4.9-14.6 months). The most common adverse events (AEs) were diarrhea (2/6), pruritis (2/6), stomatitis (1/6) and nausea (1/6). No grade 3 or more AEs were documented.

Conclusions: This study revealed that the genetic characteristics of EGFRex20ins mutations in Chinese patients with NSCLC were comparable to those reported in Caucasian patients. Furthermore, our study firstly demonstrated promising antitumor activity of osimertinib in certain EGFRex20ins mutant advanced NSCLC patients, indicating that osimertinib treatment for EGFRex20ins positive patients deserves further study.

Keywords: EGFRex20ins; NGS; NSCLC; Osimertinib.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Frequency of EGFRex20ins mutations. a. Comparison of EGFRex20ins frequency in total NSCLC patients (OrigiMed 2.3% vs. FM 1.8%, p = 0.12) and adenocarcinoma patients (OrigiMed 2.7% vs. FM 2.3%, p = 0.32). b. Comparison of EGFRex20ins frequency in EGFR-mutant NSCLC patients (OrigiMed 4.8% vs. FM 11.7%, p < 0.001) and EGFR-mutant adenocarcinoma patients (OrigiMed 4.8% vs. FM 13.9%, p < 0.001). EGFRex20ins, epidermal growth factor receptor exon 20 insertions; NSCLC, non-small cell lung cancer; FM: Foundation Medicine. * p < 0.001
Fig. 2
Fig. 2
Distribution of EGFR mutations and EGFR exon 20 mutation types and EGFRex20ins in this study. a. Distribution of EGFR mutations. b. Distribution of EGFR exon 20 mutation types and EGFRex20ins mutations
Fig. 3
Fig. 3
CT scans of the thorax performed before (baseline) and after osimertinib treatment (PR or SD). CT, computed tomography; PR, partial response; SD, stable disease
Fig. 4
Fig. 4
Maximum change in tumor size according to Response Criteria in Solid Tumors (RECIST) 1.1. Orange grid indicates partial response and gray grid stable disease
See this image and copyright information in PMC

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