Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: Distinct natural history of patients with tumors harboring the T790M mutation Journal Article


Authors: Oxnard, G. R.; Arcila, M. E.; Sima, C. S.; Riely, G. J.; Chmielecki, J.; Kris, M. G.; Pao, W.; Ladanyi, M.; Miller, V. A.
Article Title: Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: Distinct natural history of patients with tumors harboring the T790M mutation
Abstract: Purpose: Patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma develop acquired resistance to EGFR tyrosine kinase inhibitors (TKI) after a median of 10 to 16 months. In half of these cases, a second EGFR mutation, T790M, underlies acquired resistance. We undertook this study to examine the clinical course of patients harboring the T790M mutation following progression on TKI. Experimental Design: EGFR-mutant lung cancer patients with acquired resistance to EGFR TKIs were identified as part of a prospective rebiopsy protocol in which postprogression tumor specimens were collected for molecular analysis. Postprogression survival and characteristics of disease progression were compared in patients with and without T790M. Results: We identified T790M in the initial rebiopsy specimens from 58 of 93 patients (62%, 95% CI: 52-72). T790M was more common in biopsies of lung/pleura tissue and lymph nodes than in more distant sites (P = 0.014). Median postprogression survival was 16 months (interquartile range = 9-29 months); patients with T790M had a significantly longer postprogression survival (P = 0.036). Patients without T790M more often progressed in a previously uninvolved organ system (P = 0.014) and exhibited a poorer performance status at time of progression (P = 0.007). Conclusions: Among patients with acquired resistance to EGFR TKIs, the presence of T790M defines a clinical subset with a relatively favorable prognosis and more indolent progression. Knowledge of T790M status is therefore important both for the clinical care of these patients and for the optimal design and interpretation of clinical trials in this setting. ©2010 AACR.
Keywords: cancer survival; human tissue; major clinical study; clinical trial; erlotinib; cancer growth; mutant protein; epidermal growth factor receptor; lung cancer; cancer resistance; protein tyrosine kinase inhibitor; survival time; gefitinib; threonine; lung biopsy; lymph node biopsy; functional status; methionine; repeat procedure; disease activity; pleura biopsy
Journal Title: Clinical Cancer Research
Volume: 17
Issue: 6
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2011-03-15
Start Page: 1616
End Page: 1622
Language: English
DOI: 10.1158/1078-0432.ccr-10-2692
PROVIDER: scopus
PMCID: PMC3060283
PUBMED: 21135146
DOI/URL:
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 23 June 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Camelia S Sima
    204 Sima
  2. William Pao
    141 Pao
  3. Vincent Miller
    259 Miller
  4. Marc Ladanyi
    861 Ladanyi
  5. Gregory J Riely
    344 Riely
  6. Geoffrey R Oxnard
    24 Oxnard
  7. Maria Eugenia Arcila
    336 Arcila
  8. Mark Kris
    597 Kris