Dataset Information

Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations.

ABSTRACT:

Background

To characterize the effects of mutation subtypes and concomitant pathogenic mutations on progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations treated with chemotherapy.

Methods

We retrospectively found that patients who underwent genomic analysis from January 2017 to December 2019, and 101 patients with advanced EGFR ex20ins NSCLC were found. Binary logistic regression and Cox regression were used to determine how EGFR ex20ins mutation subtypes and concomitant mutations are associated with PFS and OS.

Results

A total of 8,348 patients were screened and 101 advanced EGFR ex20ins NSCLC patients were detected. Fifty-five patients who received chemotherapy (n=49) or TKIs (n=6) as first-line treatment were recorded for PFS and OS. PFS and OS were significantly longer in the platinum-based chemotherapy group (median PFS: 7.6 versus 5.6 months; P=0.001; median OS: 19.9 versus 7.4 months; P=0.027) than in the TKI group. Common mutations include Ala767_Val769dupAlaSerVal (A767_V769dupASV), Ser768_Asp770dupSerValAsp (S768_D770dupSVD) and Ala763_Tyr764insPheGlnGluAla (A763_Y764insFQEA). On binary logistic regression, common mutations (OR =17.04, 95% CI: 1.39-209.56; P=0.027) and number of concomitant mutations ≤1 (OR =34.67, 95% CI: 2.02-595.48; P=0.015) is significantly associated with durable clinical benefit (DCB). On multivariable analysis, common mutations (HR =0.26, 95% CI: 0.0.10-0.63; P=0.003) and the number of concomitant mutations ≤1 (HR =0.33, 95% CI: 0.15-0.73; P=0.006) were significantly associated with longer PFS.

Conclusions

Common mutations and the number of concomitant mutations ≤1 correlate with a biomarker that predicts benefit from chemotherapy and confers excellent prognosis for advanced patients with advanced EGFR ex20ins NSCLC. Patients with common mutations and with only one concomitant mutation had the greatest PFS and patients with uncommon mutations, and with over one concomitant mutation had the worst prognosis.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7661900 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations.

Wang Yue Y Li Jingwen J Zhou Yan Y Cao Shuhui S Ling Xuxinyi X Zhang Yao Y Nie Wei W Zhong Hua H

Annals of translational medicine 20201001 20

<h4>Background</h4>To characterize the effects of mutation subtypes and concomitant pathogenic mutations on progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations treated with chemotherapy.<h4>Methods</h4>We retrospectively found that patients who underwent genomic analysis from January 2017 to December 2019, and 101 patients with advanced EGFR ex20ins NSC ...[more]

PMID: 33209877

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Project description:BackgroundEpidermal 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.MethodsTumor 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.ResultsEGFRex20ins 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.ConclusionsThis 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.

Dataset Information

Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations.

Background

Methods

Results

Conclusions

Publications

Tumor genomics and response to chemotherapy in advanced non-small cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations.

Similar Datasets

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