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Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: Clinical outcomes and response
Background:
Epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins) represent approximately 10% of EGFR-mutant lung adenocarcinomas, and are associated with resistance to EGFR tyrosine kinase inhibitors (TKIs). Clinical outcomes in comparison with patients with sensitizing EGFR mutations are not well established.
Methods:
Patients with stage IV lung adenocarcinomas with EGFR exon20ins were identified through routine molecular testing. Clinicopathologic data were collected. Overall survival (OS) was measured from the diagnosis of stage IV disease, and in patients treated with EGFR TKIs, the time to progression (TTP) on erlotinib was measured.
Results:
One thousand eight hundred and eighty-two patients with stage IV lung adenocarcinomas were identified: 46 patients had EGFR exon20ins (2%), and 258 patients had an EGFR exon 19 deletion (exon19del)/L858R point mutation (14%). Among 11 patients with lung adenocarcinomas with EGFR exon20ins who received erlotinib, 3 patients (27%) had a partial response (FQEA, 1; ASV, 1; and unknown variant, 1). TTP for patients with EGFR exon20ins and patients with EGFR exon19del/L858R on erlotinib were 3 and 12 months, respectively (P < .01). Responses to chemotherapy were similar for patients with lung adenocarcinomas with EGFR exon20ins and patients with lung adenocarcinomas with EGFR exon19del/L858R. Median OS from the diagnosis of stage IV disease for patients with EGFR exon20ins and patients with EGFR exon19del/L858R was 26 months (95% confidence interval, 19 months-not reached n = 46) and 31 months (95% confidence interval, 28-33 months; n = 258), respectively (P = .53).
Conclusions:
The majority of patients with advanced lung adenocarcinomas harboring EGFR exon20ins do not respond to EGFR TKI therapy. Standard chemotherapy should be used as first-line therapy. These patients have an OS similar to that of patients with sensitizing EGFR mutations. Individuals with certain variants such as FQEA and ASV may respond to erlotinib.
Insights
Epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins) in lung cancer are resistant to EGFR tyrosine kinase inhibitors (TKIs). Standard chemotherapy is recommended as first-line treatment for these patients.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins) constitute about 10% of EGFR-mutant lung adenocarcinomas.
- These mutations are linked to resistance against EGFR tyrosine kinase inhibitors (TKIs).
- Clinical outcomes for patients with exon20ins compared to sensitizing EGFR mutations are not well-defined.
Purpose of the Study:
- To compare the clinical outcomes of patients with stage IV lung adenocarcinomas harboring EGFR exon20ins versus those with EGFR exon 19 deletion (exon19del)/L858R mutations.
- To evaluate the efficacy of EGFR TKIs and chemotherapy in patients with EGFR exon20ins.
Main Methods:
- Retrospective analysis of patients with stage IV lung adenocarcinomas identified via molecular testing.
- Collection of clinicopathologic data, including overall survival (OS) from stage IV diagnosis and time to progression (TTP) on erlotinib.
- Comparison of outcomes between patients with EGFR exon20ins and those with EGFR exon19del/L858R mutations.
Main Results:
- Out of 1882 patients, 46 had EGFR exon20ins (2%) and 258 had EGFR exon19del/L858R (14%).
- Among 11 patients with exon20ins treated with erlotinib, 3 (27%) showed partial response.
- TTP on erlotinib was 3 months for exon20ins versus 12 months for exon19del/L858R (P < .01).
- Chemotherapy response was similar between groups.
- Median OS was 26 months for exon20ins and 31 months for exon19del/L858R (P = .53).
Conclusions:
- Most patients with advanced lung adenocarcinoma and EGFR exon20ins do not respond to EGFR TKI therapy.
- Standard chemotherapy is recommended as the preferred first-line treatment.
- Patients with EGFR exon20ins have an OS comparable to those with sensitizing EGFR mutations.
- Certain variants like FQEA and ASV may exhibit response to erlotinib.
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