Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: Clinical outcomes and response to erlotinib Journal Article


Authors: Naidoo, J.; Sima, C. S.; Rodriguez, K.; Busby, N.; Nafa, K.; Ladanyi, M.; Riely, G. J.; Kris, M. G.; Arcila, M. E.; Yu, H. A.
Article Title: Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: Clinical outcomes and response to erlotinib
Abstract: 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. © 2015 American Cancer Society.
Keywords: cancer survival; controlled study; aged; major clinical study; overall survival; exon; gene deletion; histopathology; bevacizumab; erlotinib; advanced cancer; cancer growth; gemcitabine; cancer staging; outcome assessment; cancer immunotherapy; progression free survival; epidermal growth factor receptor; genotype; smoking; retrospective study; cetuximab; docetaxel; lung adenocarcinoma; karnofsky performance status; drug response; gefitinib; base pairing; platinum complex; taxane derivative; gene insertion; point mutation; k ras protein; pemetrexed; ethnicity; advanced; maintenance chemotherapy; nivolumab; mpdl 3280a; human; male; female; priority journal; article; pembrolizumab; epidermal growth factor receptor (egfr); exon 20 insertion
Journal Title: Cancer
Volume: 121
Issue: 18
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2015-09-15
Start Page: 3212
End Page: 3220
Language: English
DOI: 10.1002/cncr.29493
PROVIDER: scopus
PUBMED: 26096453
PMCID: PMC4807634
DOI/URL:
Notes: Export Date: 2 October 2015 -- Source: Scopus
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MSK Authors
  1. Camelia S Sima
    204 Sima
  2. Khedoudja Nafa
    181 Nafa
  3. Helena Alexandra Yu
    88 Yu
  4. Marc Ladanyi
    861 Ladanyi
  5. Gregory J Riely
    344 Riely
  6. Maria Eugenia Arcila
    336 Arcila
  7. Mark Kris
    597 Kris
  8. Natalie Rose Busby
    4 Busby
  9. Jarushka Naidoo
    30 Naidoo