Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients With Non–Small Cell Lung Cancer: A Randomized Trial

Kris, Mark G.; Natale, Ronald B.; Herbst, Roy S.; Lynch, Jr, Thomas J.; Prager, Diane; Belani, Chandra P.; Schiller, Joan H.; Kelly, Karen; Spiridonidis, Harris; Sandler, Alan; Albain, Kathy S.; Cella, David; Wolf, Michael K.; Averbuch, Steven D.; Ochs, Judith J.; Kay, Andrea C.

doi:10.1001/jama.290.16.2149

Cited by 2,517Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentHER2/EGFR in Cancer Research

Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients With Non–Small Cell Lung Cancer: A Randomized Trial

Kris, Mark G., Natale, Ronald B., Herbst, Roy S., Lynch, Jr, Thomas J., Prager, Diane, Belani, Chandra P., Schiller, Joan H., Kelly, Karen +8 more·2003·JAMA

DOI 10.1001/jama.290.16.2149

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Abstract

CONTEXT: More persons in the United States die from non-small cell lung cancer (NSCLC) than from breast, colorectal, and prostate cancer combined. In preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor (EGFR), a mediator of cell signaling, and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib. OBJECTIVE: To assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib. DESIGN, SETTING, AND PATIENTS: Double-blind, randomized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers. Patients (N = 221) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens. INTERVENTION: Daily oral gefitinib, either 500 mg (administered as two 250-mg gefitinib tablets) or 250 mg (administered as one 250-mg gefitinib tablet and 1 matching placebo). MAIN OUTCOME MEASURES: Improvement of NSCLC symptoms (2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [FACT-L] instrument) and tumor regression (>50% decrease in lesion size on imaging studies). RESULTS: Of 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250 mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving 500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial radiographic responses occurred in 12% (95% CI, 6%-20%) of individuals receiving 250 mg of gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg. Symptoms improved in 96% of patients with partial radiographic responses. The overall survival at 1 year was 25%. There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement (P =.26), radiographic tumor regression (P =.51), and projected 1-year survival (P =.54). The 500-mg dose was associated more frequently with transient acne-like rash (P =.04) and diarrhea (P =.006). CONCLUSIONS: Gefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy.

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Only 10-19% of patients with advanced non-small cell carcinoma experienced a tumor response to gefitinib.
“However, resistance gradually emerged: only 10-19% of patients with advanced non-small cell carcinoma experienced a tumor response to gefitinib;109,110”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [109]
These somatic EGFR mutations are associated with in vitro sensitivity to Gefitinib and with clinic-pathological characteristics: Asian ethnicity, female sex, adenocarcinoma histology, and never smoking status.
“These somatic mutations were associated with in vitro sensitivity to Gefitinib and with clinic-pathological characteristics preliminary associated with clinical activity [7, 8]: Asian ethnicity, female sex, adenocarcinoma histology and never smoking status.”
From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [7]

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Authors: Kris, M. G., Natale, R. B., Herbst, R. S., Lynch, Jr., Prager, D., Belani, C. P., Schiller, J. H., Kelly, K., Spiridonidis, H., Sandler, A., Albain, K. S., Cella, D., Wolf, M. K., Averbuch, S. D., Ochs, J. J., & Kay, A. C.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
Cedars-Sinai Medical Center (US)
The University of Texas MD Anderson Cancer Center (US)
University of California, Los Angeles (US)
University of Pittsburgh (US)
University of Wisconsin–Madison (US)
University of Colorado Anschutz (US)
Hematology Oncology Consultants (US)
Vanderbilt University (US)
Loyola University Chicago (US)
Northwestern University (US)
AstraZeneca (United Kingdom) (GB)
ORCID: Kris, Mark G.
Herbst, Roy S.
Belani, Chandra P.
Schiller, Joan H.
Kelly, Karen
Sandler, Alan
Albain, Kathy S.
Cella, David
Averbuch, Steven D.
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 2003-10-22
Volume: 290
Issue: 16
Pages: 2149
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.290.16.2149
OpenAlex: W2120718661
Cited by: 2,517
References: 42
Citations by year: 2026: 18 · 2025: 21 · 2024: 25 · 2023: 29 · 2022: 37 · 2021: 35 · 2020: 31 · 2019: 46 · 2018: 65 · 2017: 69 · 2016: 71 · 2015: 92 · 2014: 86 · 2013: 126 · 2012: 123
FWCI: 203.41
Type: journal article
Language: en
Open access: closed
Locations: JAMA (publishedVersion)
PubMed (publishedVersion)
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: non-small cell lung cancer, epidermal growth factor receptor, EGFR tyrosine kinase inhibitors, dose comparison, symptom response, tumor regression, radiological response, advanced lung cancer, chemotherapy-refractory cancer, oral anticancer drugs, targeted therapy, progression-free survival, quality of life
MeSH terms: Gefitinib, Administration, Oral, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Double-Blind Method, Enzyme Inhibitors, Female, Humans, Lung Neoplasms, Male, Middle Aged, Quinazolines, Radiography, Survival Analysis, Treatment Outcome, ErbB Receptors

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Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients With Non–Small Cell Lung Cancer: A Randomized Trial

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