EGFR exon 20 insertion mutations and response to osimertinib in non-small-cell lung 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. Electronic supplementary material The online version of this article (10.1186/s12885-019-5820-0) contains supplementary material, which is available to authorized users.

Comprehensive genomic profile of cholangiocarcinomas in China

“…The rapid development of NGS technologies allows for genomic profiling detection of multiple samples from different patients with multiplexed panels (21). The alignment of the sequences from tumor tissue samples and matched blood samples were considered to be an effective method for detecting somatic mutations (22)(23)(24). To date, many studies on potential biomarkers for CCA have been reported (25)(26)(27).…”

The Status of the EGFR T790M Mutation is associated with the Clinical Benefits of Osimertinib Treatment in Non-small Cell Lung Cancer Patients: A Meta-Analysis

“…Although more and more studies have confirmed the superior efficacy of Osimertinib in NSCLC paitents with EGFR driver mutations [5,12,[20][21][22], the tumor response and survival outcomes after the treatment of Osimertinib are usually different in patients. The mechanisms of resistance to Osimertinib have been the subject of several clinical studies [23][24][25].…”

Osimertinib versus afatinib in patients with T790M-positive, non-small-cell lung cancer and multiple central nervous system metastases after failure of initial EGFR-TKI treatment

“…Missing data were not included in the study, which is consistent with previous descriptions [21]. The hazard ratio (HR) and corresponding 95% CIs were estimated using Cox proportional hazards models.…”