Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Lung Cancer: Distinct Natural History of Patients with Tumors Harboring the T790M Mutation

Oxnard, Geoffrey R.; Arcila, Maria E.; Sima, Camelia S.; Riely, Gregory J.; Chmielecki, Juliann; Kris, Mark G.; Pao, William; Ladanyi, Marc; Miller, Vincent A.

doi:10.1158/1078-0432.ccr-10-2692

Cited by 627Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Lung Cancer: Distinct Natural History of Patients with Tumors Harboring the T790M Mutation

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Oxnard, Geoffrey R., Arcila, Maria E., Sima, Camelia S., Riely, Gregory J., Chmielecki, Juliann, Kris, Mark G., Pao, William, Ladanyi, Marc +1 more·2011·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-10-2692PMC PMC3060283

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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. Clin Cancer Res; 17(6); 1616–22. ©2010 AACR.

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At progression, about 60% of patients have T790M mutation in EGFR.
“At the time of progression, about 60% of patients (regardless of race or ethnic background) are found to have a p.Thr790Met point mutation (T790M) in the gene encoding EGFR.13–16”
From Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer (2017) · cites this paper as [16]

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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.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
Corresponding author: Miller, Vincent A.
ORCID: Oxnard, Geoffrey R.
Arcila, Maria E.
Riely, Gregory J.
Chmielecki, Juliann
Kris, Mark G.
Pao, William
Ladanyi, Marc
Miller, Vincent A.
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2011-03-15
Volume: 17
Issue: 6
Pages: 1616-1622
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-10-2692
PMC: PMC3060283
OpenAlex: W2138089710
Cited by: 627
References: 44
Citations by year: 2026: 15 · 2025: 18 · 2024: 16 · 2023: 31 · 2022: 23 · 2021: 54 · 2020: 59 · 2019: 51 · 2018: 64 · 2017: 58 · 2016: 47 · 2015: 40 · 2014: 38 · 2013: 56 · 2012: 39
FWCI: 29.77
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA121210, P01CA129243, R21CA115051, U54CA143798)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords: EGFR tyrosine kinase inhibitors, acquired drug resistance, EGFR-mutant lung adenocarcinoma, T790M mutation, post-progression survival, disease progression patterns, performance status, repeat biopsy, prognostic factors
MeSH terms: Adenocarcinoma, Antineoplastic Agents, Biopsy, Female, Humans, Lung Neoplasms, Male, Mutation, Prognosis, Prospective Studies, Time Factors, Disease Progression, Drug Resistance, Neoplasm, ErbB Receptors

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Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Lung Cancer: Distinct Natural History of Patients with Tumors Harboring the T790M Mutation

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