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Cited by 388Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib and Continuation Therapy Beyond Progression in EGFR -Mutant NSCLC

Open access
Le, Xiuning, Puri, Sonam, Negrao, Marcelo V., Nilsson, Monique B., Robichaux, Jacqulyne, Boyle, Theresa, Hicks, J. Kevin, Lovinger, Katherine L. +16 more·2018·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-18-1542PMC PMC6295279

Published version of a preprint

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Abstract

Purpose: Osimertinib was initially approved for T790M-positive non–small cell lung cancer (NSCLC) and, more recently, for first-line treatment of EGFR-mutant NSCLC. However, resistance mechanisms to osimertinib have been incompletely described. Experimental Design: Using cohorts from The University of Texas MD Anderson Lung Cancer Moonshot GEMINI and Moffitt Cancer Center lung cancer databases, we collected clinical data for patients treated with osimertinib. Molecular profiling analysis was performed at the time of progression in a subset of the patients. Results: In the 118 patients treated with osimertinib, 42 had molecular profiling at progression. T790M was preserved in 21 (50%) patients and lost in 21 (50%). EGFR C797 and L792 (26%) mutations were the most common resistance mechanism and were observed exclusively in T790M-preserved cases. MET amplification was the second most common alteration (14%). Recurrent alterations were observed in 22 genes/pathways, including PIK3CA, FGFR, and RET. Preclinical studies confirmed MET, PIK3CA, and epithelial-to-mesenchymal transition as potential resistance drivers. Alterations of cell-cycle genes were associated with shorter median progression-free survival (PFS, 4.4 vs. 8.8 months, P = 0.01). In 76 patients with progression, osimertinib was continued in 47 cases with a median second PFS (PFS2) of 12.6 months; 21 patients received local consolidation radiation with a median PFS of 15.5 months. Continuation of osimertinib beyond progression was associated with a longer overall survival compared with discontinuation (11.2 vs. 6.1 months, P = 0.02). Conclusions: Osimertinib resistance is associated with diverse, predominantly EGFR-independent genomic alterations. Continuation of osimertinib after progression, alone or in conjunction with radiotherapy, may provide prolonged clinical benefit in selected patients. See related commentary by Devarakonda and Govindan, p. 6112.

Integrity signals

Registry

Crossref · 10.1158/1078-0432.ccr-18-1542

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 29 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    These EGFR tertiary mutations occurred exclusively in T790M-preserved cases, not T790M-loss cases (11/19 vs 0/21, p<0.001).

    “These previously defined osimertinib-resistant EGFR mutations were exclusively observed in T790M-preserved cases; this association was statistically significant (11/19 vs. 0/21, p<0.001, Fisher exact test”
    Quote in the paperSubstantial claim
  • Findingown data

    Median PFS2 among patients continued beyond progression was 12.6 months (95% CI 8.3-15.5).

    “Median PFS2 was 12.6 months (95% CI, 8.3 to 15.5, Supple. Fig. 5)”
    Quote in the paperSubstantial claim
  • Findingown data

    Previously defined osimertinib-resistant EGFR mutations (C797S, C797G, L792H) were the most common resistance mechanism in T790M-preserved cases (11/19).

    “In the T790M-preserved group, previously defined osimertinib-resistant EGFR mutations (11/19; C797S: 8; C797G: 1; L792H: 2 [20] [21]) were the most common resistance mechanisms.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [20] Ercan, 2015, EGFR mutations and resistance to irreversible pyrimidine-based EGFR inhibitors, Clin Cancer Res source

      Not checked in the free run.

    • cites [21] Chen, 2017, Novel mutations on EGFR Leu792 potentially correlate to acquired resistance to osimertinib in advanced NSCLC, J Thorac Oncol source

      Not checked in the free run.

  • Findingown data

    Among continued patients, 21 (45%) received palliative radiation for oligometastatic progressing lesions.

    “Among the osimertinib-continued patients, 21 (45%) received palliative radiation for oligometastatic progressing lesions”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the 118-patient osimertinib-treated cohort, median progression-free survival from starting osimertinib was 8.4 months (95% CI 6.7-10.7).

    “Median PFS1 was 8.4 months (95%CI, 6.7 to 10.7, Fig. 1A)”
    Quote in the paperNot a substantial claim
  • May combine two claims. 26
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Findingown data

    Norepinephrine increased HCC827 cell proliferation in the presence of osimertinib, and propranolol restored osimertinib sensitivity.

    “In HCC827 cells, norepinephrine (10uM) significantly increased proliferation in the presence of osimertinib (from 10–50nM), suggesting resistance (red line, Fig. 3F). Propranolol (1uM), a non-selective beta-adrenergic blocker, restored osimertinib sensitivity in HCC827 cells (gray line, Fig. 3F)”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Preclinical cell line findings translate to clinical osimertinib resistance in patients.

  • May combine two claims.

    Findingown data

    Among acquired T790M cases, 19/40 (47%) preserved and 21/40 (53%) lost T790M at progression.

    “Of the acquired T790M cases, 47% (19/40) preserved and 53% (21/40) lost T790M at progression”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Among 18 platform-matched cases, 9 (50%) preserved T790M, with 6 acquiring EGFR C797S/L792H mutations.

    “Of the 18 cases, 9 (50%) preserved T790M with 6 acquired EGFR C797S/L792H mutations”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Preclinical studies confirmed MET, PIK3CA, and EMT as potential resistance drivers.

    “Preclinical studies confirmed MET, PIK3CA, and epithelial-to-mesenchymal transition (EMT) as potential resistance drivers.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Preclinical cell line findings translate to clinical osimertinib resistance in patients.

  • May combine two claims.

    Findingown data

    In HCC827 cells, an erlotinib-resistant clone ER2 with increased c-Met protein and MET copy-number gain was resistant to osimertinib but sensitive to c-met inhibitors.

    “We cultured HCC827 cells (EGFR Del745_760) in erlotinib to develop EGFR TKI resistance and identified one clone (ER2) having increased c-Met protein expression and MET copy-number gain (Fig. 3A-3B). This clone was resistant to osimertinib (Supple. Fig. 7A) without resistant mutations in the EGFR exon 20 (Supple. Fig 7C), but exquisitely sensitive to c-met inhibitors”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Preclinical cell line findings translate to clinical osimertinib resistance in patients.

  • May combine two claims.

    Findingown data

    TP53 mutation and T790M loss were not associated with PFS1 in this cohort.

    “whereas TP53 mutation and T790M loss were not (Supple. Fig. 4)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    MET amplification was the second most common resistance mechanism, observed in both T790M-preserved and T790M-loss cases (about 14%).

    “MET amplification has been reported as a mechanism of resistance to gefitinib[8] and osimertinib[23]. In our cohort, it was identified in T790M-preserved (5/19) and T790M-loss (1/21) cases, and the second most common resistance mechanism after EGFR tertiary mutations (5/42, 14%).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [8] Engelman, 2007, MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling, Science source

      Not checked in the free run.

    • cites [23] Ou, 2016, High MET amplification level as a resistance mechanism to osimertinib (AZD9291) in a patient that symptomatically responded to crizotinib treatment post-osimertinib progression, Lung Cancer source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Among 42 patients with molecular profiling at progression, T790M was preserved in 21 (50%) and lost in 21 (50%).

    “T790M was preserved in 21 (50%) patients and lost in 21 (50%).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Three patients developed treatment-related pneumonitis and two developed treatment-related cardiotoxicity.

    “Three patients developed treatment-related pneumonitis and two patients developed treatment-related cardiotoxicity with decreased ejection.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In preclinical models, PIK3CA hotspot mutation, but not BRAF, FGFR, and PDGFR overexpression alone, contributed to osimertinib resistance.

    “In our preclinical models, PIK3CA hotspot mutation, but not BRAF, FGFR, and PDGFR overexpression alone, was found to contribute to osimertinib resistance.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Preclinical cell line findings translate to clinical osimertinib resistance in patients.

  • May combine two claims.

    Findingown data

    Epinephrine reduced sensitivity of EGFR mutant cells to osimertinib in vitro, and propranolol reversed this resistance phenotype.

    “We found that epinephrine reduces the sensitivity of EGFR mutant cells to osimertinib in vitro. Beta-adrenergic blockade with propranolol reversed this resistance phenotype.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Preclinical cell line findings translate to clinical osimertinib resistance in patients.

  • May combine two claims.

    Findingown data

    Median follow-up on osimertinib was 13 months, with 63% alive at analysis.

    “Median follow-up on osimertinib was 13 months, with 63% alive at the time of analysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    One case each had FGFR3/FGFR19 amplification, MET amplification, and ERBB2 amplification.

    “one had FGFR3/FGFR19 amplification (Pt. 32, Supple Table 2), one had MET amplification (Pt. 36; FISH ratio: 7.4, Supple Table 2) and one had ERBB2 amplification (Pt. 40, Supple Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among MET-amplified patients, CDK6 and BRAF amplification were common events.

    “Among MET-amplified patients, CDK6 (4/5) and BRAF amplification (3/5) were common events”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were 14 cases without potential resistance genetic drivers, 12 in the T790M-preserved group.

    “There were 14 cases without potential resistance genetic drivers, 12 in T790M-preserved group”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Acquired PIK3CA hotspot mutations may contribute to osimertinib resistance, whereas BRAF, FGFR, or PDGFR amplifications may be passenger events or insufficient alone.

    “This data suggests that acquired PIK3CA hotspot mutations may drive contribute to osimertinib resistance, and that BRAF, FGFR, or PDGFR amplifications may be “passenger” events instead of “drivers”, or may not be able to promote resistance alone without additional concurrent alterations.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Preclinical cell line findings translate to clinical osimertinib resistance in patients.

  • May combine two claims.

    Interpretationown data

    Stress hormones induce proliferation in the presence of osimertinib, and beta-adrenergic blockade can overcome this resistance in EGFR-mutant T790M-negative lung cancer cells.

    “supporting that stress hormones induce proliferation in the presence of osimertinib. Furthermore, such resistance can be overcome through beta-adrenergic blockade in EGFR-mutant T790M-negative lung cancer cells.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Preclinical cell line findings translate to clinical osimertinib resistance in patients.

  • May combine two claims.

    Premisecitation

    Osimertinib significantly improved PFS and ORR compared with platinum-pemetrexed chemotherapy for T790M-positive NSCLC after progression on first- or second-generation EGFR-TKIs.

    “In a randomized phase III trial[3], osimertinib significantly improved both progression-free survival (PFS) and objective response rate (ORR) when compared to platinum-pemetrexed chemotherapy for T790M-positive non-small cell lung cancer (NSCLC) after progression on 1st or 2nd generation EGFR-TKIs.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Mok, 2017, Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer, N Engl J Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The study was approved by IRBs and written informed consent was obtained.

    “Written informed consents were obtained the patients, and the studies were conducted in accordance with ethical guidelines including Declaration of Helsinki and U.S. Common Rule. The study was approved by the IRBs at MDACC and University of South Florida.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    An AXL mutation was observed in one case with acquired T790M/C797S, suggesting association with EMT.

    “We observed an AXL mutation in one case with acquired T790M/C797S (Pt. 12 Supple Table 2)[24], suggesting association with EMT.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Zhang, 2012, Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer, Nat Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    EMT has been indicated as one mechanism of resistance to EGFR-TKIs.

    “Epithelial‐mesenchymal transition (EMT) has also been indicated as one mechanism of resistance to EGFR-TKIs[10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Sequist, 2011, Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors, Sci Transl Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Many patients with EGFR-mutant NSCLC might have prolonged benefit from osimertinib beyond initial progression, especially when radiation was used, suggesting a potential role for local consolidative therapy.

    “We showed that many patients with EGFR-mutant NSCLC might have prolonged benefit from osimertinib beyond their initial progression event, especially when radiation was used at progression, suggesting a potential role for local consolidative therapy in this setting.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    T790M loss is common in osimertinib-resistant cases, and T790M-loss cases show a different resistance pattern from T790M-preserved cases.

    “Furthermore, we showed that T790M loss is common in osimertinib-resistant cases, and that these cases demonstrated a different pattern of resistance compared with the T790M-preserved cases.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Osimertinib showed a significant PFS benefit compared with erlotinib or gefitinib in first-line EGFR-mutant NSCLC in the FLAURA trial.

    “when compared to erlotinib or gefitinib in the first-line setting for EGFR mutant NSCLC, osimertinib showed a significant PFS benefit in favor of osimertinib in a phase III study (FLAURA trial, NCT02296125) [4].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Soria, 2018, Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer, N Engl J Med source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Disease progression in the clinical outcome analysis was based on physician assessment and not specific formal criteria.

    “In the clinical outcome analysis, the disease progression was based on physician assessment and not specific formal criteria.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    EGFR exon 20 tertiary mutations, MET amplification, HER2 amplification, small cell transformation, and EMT are possible drivers of resistance.

    “Reports on individual cases or clinical series have demonstrated that EGFR exon 20 tertiary mutations, including C797S[5–7], MET amplification[8], HER2 amplification[9], small cell transformation[10], and epithelial-mesenchymal transition (EMT) [10, 11] are possible drivers of resistance.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [5] Thress, 2015, Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M, Nat Med source

      Not checked in the free run.

    • cites [6] Yang, 2018, Investigating novel resistance mechanisms to third-generation EGFR tyrosine kinase inhibitor osimertinib in non-small cell lung cancer patients, Clin Cancer Res source

      Not checked in the free run.

    • cites [7] Oxnard, 2018, Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib, JAMA Oncol source

      Not checked in the free run.

    • cites [8] Engelman, 2007, MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling, Science source

      Not checked in the free run.

    • cites [9] Takezawa, 2012, HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation, Cancer Discov source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Because CDK6, MET, and BRAF are close on chromosome 7q, it is possible these amplifications arose from a single genomic event.

    “Because of the relative proximity of the three genes in chromosome 7q (CDK6 at Chr7q21.2, MET at Chr7q31.2 BRAF at Chr7q34), it is possible that these amplifications arose from a single genomic event.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    In some cases different platforms were used for pre-treatment and post-progression profiling; platform-matched analysis showed similar results to the overall analysis.

    “In the genetic profiling analysis, in some cases different platforms were used for the pre-treatment and post-progression profiling; however, analysis of the platform-matched cases shows similar results as the overall analysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The majority of patients received osimertinib as second- or later-line therapy, with only six receiving it first-line.

    “the majority of the patients in our cohort received osimertinib as second- or later-lines of therapy (Table 1), with only six patients with baseline EGFR T790M or germline T790M receiving osimertinib as the first-line treatment”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    In most T790M-preserved cases, resistance involves continued EGFR activation through tertiary mutations or bypass signaling, whereas T790M-loss cases use diverse, predominantly EGFR-independent mechanisms.

    “Specifically, in most of the T790M-preserved cases, resistance is associated with continued EGFR activation through known resistance tertiary mutations (e.g. C797S) or activation of bypass signaling pathways, whereas resistance in T790M-loss cases occurs through diverse, and predominantly EGFR-independent mechanisms.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Stress hormone induced beta adrenergic pathway activation has been identified as a driver of resistance to first-generation TKIs and can be overcome by beta-adrenergic blockade.

    “Stress hormone induced beta adrenergic pathway activation has recently been identified as a driver of resistance to first-generation TKIs and can be overcome by beta-adrenergic blockade[25]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Nilsson, 2017, Stress hormones promote EGFR inhibitor resistance in NSCLC: implications for combinations with beta-blockers, Sci Transl Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    T790M-preserved and T790M-loss groups had similar frequency of NGS-based panel tests (14/19 vs 15/21, p=0.87).

    “Both T790M-preserved and -loss groups had similar frequency with next-generation sequencing based paneled tests (14/19 vs. 15/21, Chi-Square p=0.87).”
    Quote in the paperNot a substantial claim
32 of 32

  • The paper relies on this without support.

    The molecular alterations detected in the 42 profiled patients are representative of resistance mechanisms in the broader osimertinib-treated cohort.

    “Genomic profiling at the time of progression was available for 42 patients”
    “The 18 platform-matched cases represent the common resistance mechanisms seen in our 42 cases cohort”

  • The paper relies on this without support.

    Preclinical cell line findings translate to clinical osimertinib resistance in patients.

    “Taken together, these preclinical data provide evidence that EGFR-independent mechanisms of resistance observed for first- and second-generation EGFR TKIs (MET amplification, PIK3CA mutation, EMT, beta adrenergic activation) may promote osimertinib resistance as well.”

  • The paper relies on this without support.

    The historical median OS of 19–28 months with first- or second-generation EGFR TKIs is a valid comparator for this cohort's OS from diagnosis.

    “a strikingly long survival compared to median OS of 19–28 months with first- or second-generation EGFR TKIs[17–19].”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • T790M-like-3R mutants, complex mutations comprising T790M and a known drug-resistance mutation, were resistant to classical EGFR TKIs but retained selectivity for select ALK and PKC inhibitors such as brigatinib or midostaurin.

    “T790M-like-3R mutants, complex mutations comprising T790M and a known drug-resistance mutation (that is, C797S30, L718X31 or L792H18,31), were resistant to classical EGFR TKIs but retained selectivity for select ALK and PKC inhibitors such as brigatinib or midostaurin (Extended Data Fig. 7c).”

    From Structure-based classification predicts drug response in EGFR-mutant NSCLC (2021) · cites this paper as [18]

  • EGFR mutations were determined from formalin-fixed paraffin-embedded tumours or digital-droplet PCR for blood samples by CLIA-certified methods.

    “EGFR mutations were determined from formalin-fixed paraffin-embedded tumours or digital-droplet PCR for blood samples by CLIA-certified methods as previously described18,37.”

    From Structure-based classification predicts drug response in EGFR-mutant NSCLC (2021) · cites this paper as [18]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Too many T790M-preserved cases are classified as driverless

    Minor

    The paper places 12 cases without potential resistance genetic drivers in the T790M-preserved group, but also identifies resistance-associated EGFR mutations in 11 of that group's 19 cases. Those categories require at least 23 distinct cases in a group of 19.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Oxnard, 2017, Osimertinib resistance mediated by loss of EGFR T790M is associated with early resistance and competing resistance mechanisms, S1767

Cited by

Sorted by citations

Related

Authors
Le, X., Puri, S., Negrao, M. V., Nilsson, M. B., Robichaux, J., Boyle, T., Hicks, J. K., Lovinger, K. L., Roarty, E., Rinsurongkawong, W., Tang, M., Sun, H., Elamin, Y., Lacerda, L. C., Lewis, J., Roth, J. A., Swisher, S. G., Lee, J. J., William, W. N., Glisson, B. S., Zhang, J., Papadimitrakopoulou, V. A., Gray, J. E., & Heymach, J. V.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • Moffitt Cancer Center (US)
Corresponding author
  • Gray, Jhanelle E.
  • Heymach, John V.
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2018-12-13
Volume
24
Issue
24
Pages
6195-6203
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-18-1542
PMC
PMC6295279
OpenAlex
W2891909134
Cited by
387
References
34
Citations by year
2026: 20 · 2025: 41 · 2024: 33 · 2023: 51 · 2022: 63 · 2021: 68 · 2020: 56 · 2019: 50 · 2018: 5
FWCI
33.69
Type
journal article
Language
en
Open access
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • MD Anderson Cancer Center (P30 CA01667)
  • NIH (R01 CA190628)
  • UT Lung SPORE (P50 CA70907)
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
osimertinib, EGFR-mutant non-small cell lung cancer, drug resistance mechanisms, T790M mutation, MET amplification, PIK3CA, fibroblast growth factor receptor, RET, epithelial-mesenchymal transition, cell cycle genes, progression-free survival, consolidation radiotherapy, overall survival
MeSH terms
Acrylamides, Adult, Aged, Aniline Compounds, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Female, Humans, Indoles, Lung Neoplasms, Male, Middle Aged, Mutation, Prognosis, Pyrimidines, Retrospective Studies, Survival Analysis, Treatment Outcome, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, Kaplan-Meier Estimate, Molecular Targeted Therapy, ErbB Receptors

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