Gefitinib versus placebo in completely resected non-small-cell lung cancer: Results of the NCIC CTG BR19 study

Glenwood D. Goss, Chris O'Callaghan, Ian Lorimer, Ming Sound Tsao, Gregory A. Masters, James Jett, Martin J. Edelman, Rogerio Lilenbaum, Hak Choy, Fadlo Khuri, Katherine Pisters, David R Gandara, Kemp Kernstine, Charles Butts, Jonathan Noble, Thomas A. Hensing, Kendrith Rowland, Joan Schiller, Keyue Ding, Frances A. Shepherd

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Purpose Survival of patients with completely resected non-small-cell lung cancer (NSCLC) is unsatisfactory, and in 2002, the benefit of adjuvant chemotherapy was not established. This phase III study assessed the impact of postoperative adjuvant gefitinib on overall survival (OS). Patients and Methods Patients with completely resected (stage IB, II, or IIIA) NSCLC stratified by stage, histology, sex, postoperative radiotherapy, and chemotherapy were randomly assigned (1:1) to receive gefitinib 250 mg per day or placebo for 2 years. Study end points were OS, disease-free survival (DFS), and toxicity. Results As a result of early closure, 503 of 1,242 planned patients were randomly assigned (251 to gefitinib and 252 to placebo). Baseline factors were balanced between the arms. With a median of 4.7 years of follow-up (range, 0.1 to 6.3 years), there was no difference in OS (hazard ratio [HR], 1.24; 95% CI, 0.94 to 1.64; P = .14) or DFS (HR, 1.22; 95% CI, 0.93 to 1.61; P = .15) between the arms. Exploratory analyses demonstrated no DFS (HR, 1.28; 95% CI, 0.92 to 1.76; P = .14) or OS benefit (HR, 1.24; 95% CI, 0.90 to 1.71; P = .18) from gefitinib for 344 patients with epidermal growth factor receptor (EGFR) wild-type tumors. Similarly, there was no DFS (HR, 1.84; 95% CI, 0.44 to 7.73; P = .395) or OS benefit (HR, 3.16; 95% CI, 0.61 to 16.45; P = .15) from gefitinib for the 15 patients with EGFR mutation-positive tumors. Adverse events were those expected with an EGFR inhibitor. Serious adverse events occurred in ≤ 5% of patients, except infection, fatigue, and pain. One patient in each arm had fatal pneumonitis. Conclusion Although the trial closed prematurely and definitive statements regarding the efficacy of adjuvant gefitinib cannot be made, these results indicate that it is unlikely to be of benefit.

Original languageEnglish (US)
Pages (from-to)3320-3326
Number of pages7
JournalJournal of Clinical Oncology
Volume31
Issue number27
DOIs
StatePublished - Sep 20 2013

Fingerprint

Non-Small Cell Lung Carcinoma
Placebos
Disease-Free Survival
Survival
Epidermal Growth Factor Receptor
gefitinib
Adjuvant Chemotherapy
Fatigue
Neoplasms
Pneumonia
Histology
Radiotherapy
Drug Therapy
Pain
Mutation
Infection

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Goss, G. D., O'Callaghan, C., Lorimer, I., Tsao, M. S., Masters, G. A., Jett, J., ... Shepherd, F. A. (2013). Gefitinib versus placebo in completely resected non-small-cell lung cancer: Results of the NCIC CTG BR19 study. Journal of Clinical Oncology, 31(27), 3320-3326. https://doi.org/10.1200/JCO.2013.51.1816

Gefitinib versus placebo in completely resected non-small-cell lung cancer : Results of the NCIC CTG BR19 study. / Goss, Glenwood D.; O'Callaghan, Chris; Lorimer, Ian; Tsao, Ming Sound; Masters, Gregory A.; Jett, James; Edelman, Martin J.; Lilenbaum, Rogerio; Choy, Hak; Khuri, Fadlo; Pisters, Katherine; Gandara, David R; Kernstine, Kemp; Butts, Charles; Noble, Jonathan; Hensing, Thomas A.; Rowland, Kendrith; Schiller, Joan; Ding, Keyue; Shepherd, Frances A.

In: Journal of Clinical Oncology, Vol. 31, No. 27, 20.09.2013, p. 3320-3326.

Research output: Contribution to journalArticle

Goss, GD, O'Callaghan, C, Lorimer, I, Tsao, MS, Masters, GA, Jett, J, Edelman, MJ, Lilenbaum, R, Choy, H, Khuri, F, Pisters, K, Gandara, DR, Kernstine, K, Butts, C, Noble, J, Hensing, TA, Rowland, K, Schiller, J, Ding, K & Shepherd, FA 2013, 'Gefitinib versus placebo in completely resected non-small-cell lung cancer: Results of the NCIC CTG BR19 study', Journal of Clinical Oncology, vol. 31, no. 27, pp. 3320-3326. https://doi.org/10.1200/JCO.2013.51.1816
Goss, Glenwood D. ; O'Callaghan, Chris ; Lorimer, Ian ; Tsao, Ming Sound ; Masters, Gregory A. ; Jett, James ; Edelman, Martin J. ; Lilenbaum, Rogerio ; Choy, Hak ; Khuri, Fadlo ; Pisters, Katherine ; Gandara, David R ; Kernstine, Kemp ; Butts, Charles ; Noble, Jonathan ; Hensing, Thomas A. ; Rowland, Kendrith ; Schiller, Joan ; Ding, Keyue ; Shepherd, Frances A. / Gefitinib versus placebo in completely resected non-small-cell lung cancer : Results of the NCIC CTG BR19 study. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 27. pp. 3320-3326.
@article{d8d67f43346a42c592ea0a736f919c71,
title = "Gefitinib versus placebo in completely resected non-small-cell lung cancer: Results of the NCIC CTG BR19 study",
abstract = "Purpose Survival of patients with completely resected non-small-cell lung cancer (NSCLC) is unsatisfactory, and in 2002, the benefit of adjuvant chemotherapy was not established. This phase III study assessed the impact of postoperative adjuvant gefitinib on overall survival (OS). Patients and Methods Patients with completely resected (stage IB, II, or IIIA) NSCLC stratified by stage, histology, sex, postoperative radiotherapy, and chemotherapy were randomly assigned (1:1) to receive gefitinib 250 mg per day or placebo for 2 years. Study end points were OS, disease-free survival (DFS), and toxicity. Results As a result of early closure, 503 of 1,242 planned patients were randomly assigned (251 to gefitinib and 252 to placebo). Baseline factors were balanced between the arms. With a median of 4.7 years of follow-up (range, 0.1 to 6.3 years), there was no difference in OS (hazard ratio [HR], 1.24; 95{\%} CI, 0.94 to 1.64; P = .14) or DFS (HR, 1.22; 95{\%} CI, 0.93 to 1.61; P = .15) between the arms. Exploratory analyses demonstrated no DFS (HR, 1.28; 95{\%} CI, 0.92 to 1.76; P = .14) or OS benefit (HR, 1.24; 95{\%} CI, 0.90 to 1.71; P = .18) from gefitinib for 344 patients with epidermal growth factor receptor (EGFR) wild-type tumors. Similarly, there was no DFS (HR, 1.84; 95{\%} CI, 0.44 to 7.73; P = .395) or OS benefit (HR, 3.16; 95{\%} CI, 0.61 to 16.45; P = .15) from gefitinib for the 15 patients with EGFR mutation-positive tumors. Adverse events were those expected with an EGFR inhibitor. Serious adverse events occurred in ≤ 5{\%} of patients, except infection, fatigue, and pain. One patient in each arm had fatal pneumonitis. Conclusion Although the trial closed prematurely and definitive statements regarding the efficacy of adjuvant gefitinib cannot be made, these results indicate that it is unlikely to be of benefit.",
author = "Goss, {Glenwood D.} and Chris O'Callaghan and Ian Lorimer and Tsao, {Ming Sound} and Masters, {Gregory A.} and James Jett and Edelman, {Martin J.} and Rogerio Lilenbaum and Hak Choy and Fadlo Khuri and Katherine Pisters and Gandara, {David R} and Kemp Kernstine and Charles Butts and Jonathan Noble and Hensing, {Thomas A.} and Kendrith Rowland and Joan Schiller and Keyue Ding and Shepherd, {Frances A.}",
year = "2013",
month = "9",
day = "20",
doi = "10.1200/JCO.2013.51.1816",
language = "English (US)",
volume = "31",
pages = "3320--3326",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "27",

}

TY - JOUR

T1 - Gefitinib versus placebo in completely resected non-small-cell lung cancer

T2 - Results of the NCIC CTG BR19 study

AU - Goss, Glenwood D.

AU - O'Callaghan, Chris

AU - Lorimer, Ian

AU - Tsao, Ming Sound

AU - Masters, Gregory A.

AU - Jett, James

AU - Edelman, Martin J.

AU - Lilenbaum, Rogerio

AU - Choy, Hak

AU - Khuri, Fadlo

AU - Pisters, Katherine

AU - Gandara, David R

AU - Kernstine, Kemp

AU - Butts, Charles

AU - Noble, Jonathan

AU - Hensing, Thomas A.

AU - Rowland, Kendrith

AU - Schiller, Joan

AU - Ding, Keyue

AU - Shepherd, Frances A.

PY - 2013/9/20

Y1 - 2013/9/20

N2 - Purpose Survival of patients with completely resected non-small-cell lung cancer (NSCLC) is unsatisfactory, and in 2002, the benefit of adjuvant chemotherapy was not established. This phase III study assessed the impact of postoperative adjuvant gefitinib on overall survival (OS). Patients and Methods Patients with completely resected (stage IB, II, or IIIA) NSCLC stratified by stage, histology, sex, postoperative radiotherapy, and chemotherapy were randomly assigned (1:1) to receive gefitinib 250 mg per day or placebo for 2 years. Study end points were OS, disease-free survival (DFS), and toxicity. Results As a result of early closure, 503 of 1,242 planned patients were randomly assigned (251 to gefitinib and 252 to placebo). Baseline factors were balanced between the arms. With a median of 4.7 years of follow-up (range, 0.1 to 6.3 years), there was no difference in OS (hazard ratio [HR], 1.24; 95% CI, 0.94 to 1.64; P = .14) or DFS (HR, 1.22; 95% CI, 0.93 to 1.61; P = .15) between the arms. Exploratory analyses demonstrated no DFS (HR, 1.28; 95% CI, 0.92 to 1.76; P = .14) or OS benefit (HR, 1.24; 95% CI, 0.90 to 1.71; P = .18) from gefitinib for 344 patients with epidermal growth factor receptor (EGFR) wild-type tumors. Similarly, there was no DFS (HR, 1.84; 95% CI, 0.44 to 7.73; P = .395) or OS benefit (HR, 3.16; 95% CI, 0.61 to 16.45; P = .15) from gefitinib for the 15 patients with EGFR mutation-positive tumors. Adverse events were those expected with an EGFR inhibitor. Serious adverse events occurred in ≤ 5% of patients, except infection, fatigue, and pain. One patient in each arm had fatal pneumonitis. Conclusion Although the trial closed prematurely and definitive statements regarding the efficacy of adjuvant gefitinib cannot be made, these results indicate that it is unlikely to be of benefit.

AB - Purpose Survival of patients with completely resected non-small-cell lung cancer (NSCLC) is unsatisfactory, and in 2002, the benefit of adjuvant chemotherapy was not established. This phase III study assessed the impact of postoperative adjuvant gefitinib on overall survival (OS). Patients and Methods Patients with completely resected (stage IB, II, or IIIA) NSCLC stratified by stage, histology, sex, postoperative radiotherapy, and chemotherapy were randomly assigned (1:1) to receive gefitinib 250 mg per day or placebo for 2 years. Study end points were OS, disease-free survival (DFS), and toxicity. Results As a result of early closure, 503 of 1,242 planned patients were randomly assigned (251 to gefitinib and 252 to placebo). Baseline factors were balanced between the arms. With a median of 4.7 years of follow-up (range, 0.1 to 6.3 years), there was no difference in OS (hazard ratio [HR], 1.24; 95% CI, 0.94 to 1.64; P = .14) or DFS (HR, 1.22; 95% CI, 0.93 to 1.61; P = .15) between the arms. Exploratory analyses demonstrated no DFS (HR, 1.28; 95% CI, 0.92 to 1.76; P = .14) or OS benefit (HR, 1.24; 95% CI, 0.90 to 1.71; P = .18) from gefitinib for 344 patients with epidermal growth factor receptor (EGFR) wild-type tumors. Similarly, there was no DFS (HR, 1.84; 95% CI, 0.44 to 7.73; P = .395) or OS benefit (HR, 3.16; 95% CI, 0.61 to 16.45; P = .15) from gefitinib for the 15 patients with EGFR mutation-positive tumors. Adverse events were those expected with an EGFR inhibitor. Serious adverse events occurred in ≤ 5% of patients, except infection, fatigue, and pain. One patient in each arm had fatal pneumonitis. Conclusion Although the trial closed prematurely and definitive statements regarding the efficacy of adjuvant gefitinib cannot be made, these results indicate that it is unlikely to be of benefit.

UR - http://www.scopus.com/inward/record.url?scp=84890896341&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890896341&partnerID=8YFLogxK

U2 - 10.1200/JCO.2013.51.1816

DO - 10.1200/JCO.2013.51.1816

M3 - Article

C2 - 23980091

AN - SCOPUS:84890896341

VL - 31

SP - 3320

EP - 3326

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 27

ER -