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Cited by 17Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentHER2/EGFR in Cancer Research

Revisiting Clinical Trials Using EGFR Inhibitor-Based Regimens in Patients with Advanced Non-Small Cell Lung Cancer: A Retrospective Analysis of an MD Anderson Cancer Center Phase I Population

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Wheler, Jennifer, Falchook, Gerald, Tsimberidou, Apostolia M., Hong, David, Naing, Aung, Piha-Paul, Sarina, Chen, Su S., Heymach, John +5 more·2013·Oncotarget
DOI 10.18632/oncotarget.1028PMC PMC3742837
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Abstract

// Jennifer Wheler 1 , Gerald Falchook 1 , Apostolia M. Tsimberidou 1 , David Hong 1 , Aung Naing 1 , Sarina Piha-Paul 1 , Su S. Chen 2 , John Heymach 3 , Siqing Fu 1 , Bettzy Stephen 1 , Jansina Y. Fok 1 , Filip Janku 1 , Razelle Kurzrock 4 1 Department of Investigational Cancer Therapeutics – a Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Texas 2 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Texas 3 Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Texas 4 Moores Cancer Center, University of California, San Diego Correspondence: Jennifer Wheler, email: // Keywords : EGFR mutation, EGFR wild-type, non-small cell lung cancer, phase I trials, resistance, squamous cell Received : May 10, 2013 Accepted : June 2, 2013 Published : June 4, 2013 Abstract Purpose: Single-agent EGFR inhibitor therapy is effective mainly in patients with lung cancer and EGFR mutations. Treating patients who develop resistance, or who are insensitive from the outset, often because of resistant mutations, other aberrations or the lack of an EGFR mutation, probably requires rational combinations. We therefore investigated the outcome of EGFR inhibitor-based combination regimens in patients with heavily-pretreated non-small cell lung cancer (NSCLC) referred to a Phase I Clinic. Methods: We reviewed the electronic records of patients with NSCLC treated with an EGFR inhibitor-based combination regimen: erlotinib and cetuximab; erlotinib, cetuximab and bevacizumab; erlotinib and dasatinib; erlotinib and bortezomib; or cetuximab and sirolimus. Results: EGFR mutations were detected in 16% of patients (21/131). EGFR inhibitor-based combination regimens were administered to 15 patients with EGFR -mutant NSCLC and 24 with EGFR wild-type disease. Stable disease (SD) ≥6 months/partial remission (PR) was attained in 20% of EGFR -mutant patients (3/15; two with sensitive mutations and secondary resistance to prior erlotinib, and one with a resistant mutation), as well as 26% of evaluable patients (5/19) with wild-type disease. One of three evaluable patients with squamous cell histology achieved SD for 26.5 months ( EGFR wild-type, TP53 -mutant, regimen=erlotinib, cetuximab and bevacizumab). Conclusions: Eight of 34 evaluable patients (24%) with advanced, refractory NSCLC evaluable for response achieved SD ≥6 months/PR (PR=3; SD ≥6 months=5) on EGFR inhibitor-based combination regimens (erlotinib, cetuximab; erlotinib, cetuximab and bevacizumab; and, erlotinib, bortezomib), including patients with secondary resistance to single-agent EGFR inhibitors, resistant mutations, wild-type disease, and, squamous histology.

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  • In previously published clinical studies, patients with only a single amino acid insertion responded better to already-established therapies, such as erlotinib plus cetuximab or irreversible inhibitors, compared to patients with larger insertions comprised of three amino acids.

    “In previously published clinical studies, patients with only a single amino acid insertion responded better to already-established therapies, such as erlotinib plus cetuximab or irreversible inhibitors, compared to patients with larger insertions comprised of three amino acids48,49,50.”

    From Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non–small cell lung cancer (2018) · cites this paper as [49]

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Authors
Wheler, J., Falchook, G., Tsimberidou, A. M., Hong, D., Naing, A., Piha-Paul, S., Chen, S. S., Heymach, J., Fu, S., Stephen, B., Fok, J. Y., Janku, F., & Kurzrock, R.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • Department of Investigational Cancer Therapeutics - a Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Texas
  • University of California San Diego (US)
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2013-05-31
Volume
4
Issue
5
Pages
772-784
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.1028
PMC
PMC3742837
OpenAlex
W2129881382
Cited by
17
References
52
Citations by year
2022: 1 · 2021: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 5 · 2014: 1 · 2013: 3
FWCI
2.72
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
National Cancer Institute (P30CA016672)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Keywords
EGFR inhibitors, EGFR mutation, EGFR wild-type, erlotinib, cetuximab, bevacizumab, dasatinib, bortezomib, rapamycin, combination therapy, drug resistance, heavily pretreated patients, treatment response, progression-free survival, EGFR tyrosine kinase
MeSH terms
Bevacizumab, Cetuximab, Bortezomib, Erlotinib Hydrochloride, Dasatinib, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Boronic Acids, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Pyrazines, Pyrimidines, Quinazolines, Retrospective Studies, Survival, Thiazoles, Treatment Outcome, Sirolimus, Angiogenesis Inhibitors, Protein Kinase Inhibitors, Antibodies, Monoclonal, Humanized, ErbB Receptors

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