Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2

Abstract

Unlike common epidermal growth factor receptor gene (EGFR) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene (HER2) are associated with insensitivity to EGFR-TKIs, with treatment options for patients with such mutations being limited. Clinical characteristics, outcome of EGFR-TKI or nivolumab treatment, and the presence of coexisting mutations were reviewed for NSCLC patients with exon-20 mutations of EGFR or HER2 as detected by routine application of an amplicon-based next-generation sequencing panel. Between July 2013 and June 2017, 206 patients with pathologically confirmed lung cancer were screened for genetic alterations including HER2 and EGFR mutations. Ten patients harbored HER2 exon-20 insertions (one of whom also carried an exon-19 deletion of EGFR), and 12 patients harbored EGFR exon-20 mutations. Five of the 13 patients with EGFR mutations were treated with EGFR-TKIs, two of whom manifested a partial response, two stable disease, and one progressive disease. Among the seven patients treated with nivolumab, one patient manifested a partial response, three stable disease, and three progressive disease, with most (86%) of these patients discontinuing treatment as a result of disease progression within 4 months. The H1047R mutation of PIK3CA detected in one patient was the only actionable mutation coexisting with the exon-20 mutations of EGFR or HER2. Potentially actionable mutations thus rarely coexist with exon-20 mutations of EGFR or HER2, and EGFR-TKIs and nivolumab show limited efficacy in patients with such exon-20 mutations.

Keywords: epidermal growth factor receptor gene (EGFR); human epidermal growth factor receptor 2 gene (HER2); lung cancer; nivolumab; resistance.

Figure 1. Somatic gene mutations detected with an NGS panel covering 22 genes in lung cancer specimens positive for exon-20 mutations of EGFR or HER2

Each column corresponds to one of the 22 patients.

Figure 2. Swimmer plot for duration of disease stability or response to EGFR-TKI treatment in patients with exon-20 mutations of EGFR or HER2

Bar length indicates the duration of EGFR-TKI treatment for each patient, with the best response observed before treatment failure indicated on the right. The origin corresponds to treatment start date, and the arrow indicates an ongoing response at the time of data censoring.

Figure 3. Swimmer plot for duration of disease stability or response to nivolumab treatment in patients with exon-20 mutations of EGFR or HER2

Bar length indicates the duration of nivolumab treatment for each patient, with the best response observed before treatment failure indicated on the right. The origin corresponds to treatment start date, and the arrow indicates an ongoing response at the time of data censoring. The TPS for PD-L1 expression in tumor specimens is indicated at the far right. NA, not assessed.