Adjuvant erlotinib versus placebo in patients with stage IB-IIIA nonsmall-cell lung cancer (RADIANT)

A randomized, double-blind, Phase III trial

Karen Kelly, Nasser K. Altorki, Wilfried E E Eberhardt, Mary E R OBrien, David R. Spigel, Lucio Crinò, Chun Ming Tsai, Joo Hang Kim, Eun Kyung Cho, Philip C. Hoffman, Sergey V. Orlov, Piotr Serwatowski, Jiuzhou Wang, Margaret A. Foley, Julie D. Horan, Frances A. Shepherd

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Purpose Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have proven efficacy in advanced nonsmall-cell lung cancer (NSCLC). We hypothesized that erlotinib would be efficacious in the adjuvant setting. Patients and Methods An international randomized, double-blind, placebo-controlled study was conducted in patients with completely resected IB to IIIA NSCLC whose tumors expressed EGFR protein by immunohistochemistry or EGFR amplification by fluorescence in situ hybridization. Patients were assigned 2:1 to erlotinib 150 mg once per day or placebo for 2 years. Stratification factors were stage, histology, previous adjuvant chemotherapy, smoking status, EGFR amplification status, and country. The primary end point was disease-free survival (DFS); key secondary end points were overall survival (OS) and DFS and OS in patients whose tumors had EGFR-activating mutations (EGFRm-positive). Results A total of 973 patients were randomly assigned (November 26, 2007, to July 7, 2010). There was no statistically significant difference in DFS (median, 50.5 months for erlotinib and 48.2 months for placebo; hazard ratio, 0.90; 95% CI, 0.74 to 1.10; P = .324). Among the 161 patients (16.5%) in the EGFRm-positive subgroup, DFS favored erlotinib (median, 46.4 v 28.5 months; hazard ratio, 0.61; 95% CI, 0.38 to 0.98; P = .039), but this was not statistically significant because of the hierarchical testing procedure. OS data are immature. Rash and diarrhea were common adverse events occurring in 528 (86.4%) and 319 (52.2%) patients treated with erlotinib, respectively, versus 110 (32.1%) and 54 (15.7%) patients receiving placebo. The most common grade 3 adverse events in patients treated with erlotinib were rash (22.3%) and diarrhea (6.2%). Conclusion Adjuvant erlotinib did not prolong DFS in patients with EGFR-expressing NSCLC or in the EGFRm-positive subgroup. Further evaluation of erlotinib is warranted in the EGFRmpositive subgroup.

Original languageEnglish (US)
Pages (from-to)4007-4014
Number of pages8
JournalJournal of Clinical Oncology
Volume33
Issue number34
DOIs
StatePublished - Dec 1 2015

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Non-Small Cell Lung Carcinoma
Placebos
Epidermal Growth Factor Receptor
Disease-Free Survival
Exanthema
Survival
Diarrhea
Erlotinib Hydrochloride
Adjuvant Chemotherapy
Fluorescence In Situ Hybridization
Protein-Tyrosine Kinases
Neoplasms
Histology
Smoking
Immunohistochemistry
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Adjuvant erlotinib versus placebo in patients with stage IB-IIIA nonsmall-cell lung cancer (RADIANT) : A randomized, double-blind, Phase III trial. / Kelly, Karen; Altorki, Nasser K.; Eberhardt, Wilfried E E; OBrien, Mary E R; Spigel, David R.; Crinò, Lucio; Tsai, Chun Ming; Kim, Joo Hang; Cho, Eun Kyung; Hoffman, Philip C.; Orlov, Sergey V.; Serwatowski, Piotr; Wang, Jiuzhou; Foley, Margaret A.; Horan, Julie D.; Shepherd, Frances A.

In: Journal of Clinical Oncology, Vol. 33, No. 34, 01.12.2015, p. 4007-4014.

Research output: Contribution to journalArticle

Kelly, K, Altorki, NK, Eberhardt, WEE, OBrien, MER, Spigel, DR, Crinò, L, Tsai, CM, Kim, JH, Cho, EK, Hoffman, PC, Orlov, SV, Serwatowski, P, Wang, J, Foley, MA, Horan, JD & Shepherd, FA 2015, 'Adjuvant erlotinib versus placebo in patients with stage IB-IIIA nonsmall-cell lung cancer (RADIANT): A randomized, double-blind, Phase III trial', Journal of Clinical Oncology, vol. 33, no. 34, pp. 4007-4014. https://doi.org/10.1200/JCO.2015.61.8918
Kelly, Karen ; Altorki, Nasser K. ; Eberhardt, Wilfried E E ; OBrien, Mary E R ; Spigel, David R. ; Crinò, Lucio ; Tsai, Chun Ming ; Kim, Joo Hang ; Cho, Eun Kyung ; Hoffman, Philip C. ; Orlov, Sergey V. ; Serwatowski, Piotr ; Wang, Jiuzhou ; Foley, Margaret A. ; Horan, Julie D. ; Shepherd, Frances A. / Adjuvant erlotinib versus placebo in patients with stage IB-IIIA nonsmall-cell lung cancer (RADIANT) : A randomized, double-blind, Phase III trial. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 34. pp. 4007-4014.
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title = "Adjuvant erlotinib versus placebo in patients with stage IB-IIIA nonsmall-cell lung cancer (RADIANT): A randomized, double-blind, Phase III trial",
abstract = "Purpose Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have proven efficacy in advanced nonsmall-cell lung cancer (NSCLC). We hypothesized that erlotinib would be efficacious in the adjuvant setting. Patients and Methods An international randomized, double-blind, placebo-controlled study was conducted in patients with completely resected IB to IIIA NSCLC whose tumors expressed EGFR protein by immunohistochemistry or EGFR amplification by fluorescence in situ hybridization. Patients were assigned 2:1 to erlotinib 150 mg once per day or placebo for 2 years. Stratification factors were stage, histology, previous adjuvant chemotherapy, smoking status, EGFR amplification status, and country. The primary end point was disease-free survival (DFS); key secondary end points were overall survival (OS) and DFS and OS in patients whose tumors had EGFR-activating mutations (EGFRm-positive). Results A total of 973 patients were randomly assigned (November 26, 2007, to July 7, 2010). There was no statistically significant difference in DFS (median, 50.5 months for erlotinib and 48.2 months for placebo; hazard ratio, 0.90; 95{\%} CI, 0.74 to 1.10; P = .324). Among the 161 patients (16.5{\%}) in the EGFRm-positive subgroup, DFS favored erlotinib (median, 46.4 v 28.5 months; hazard ratio, 0.61; 95{\%} CI, 0.38 to 0.98; P = .039), but this was not statistically significant because of the hierarchical testing procedure. OS data are immature. Rash and diarrhea were common adverse events occurring in 528 (86.4{\%}) and 319 (52.2{\%}) patients treated with erlotinib, respectively, versus 110 (32.1{\%}) and 54 (15.7{\%}) patients receiving placebo. The most common grade 3 adverse events in patients treated with erlotinib were rash (22.3{\%}) and diarrhea (6.2{\%}). Conclusion Adjuvant erlotinib did not prolong DFS in patients with EGFR-expressing NSCLC or in the EGFRm-positive subgroup. Further evaluation of erlotinib is warranted in the EGFRmpositive subgroup.",
author = "Karen Kelly and Altorki, {Nasser K.} and Eberhardt, {Wilfried E E} and OBrien, {Mary E R} and Spigel, {David R.} and Lucio Crin{\`o} and Tsai, {Chun Ming} and Kim, {Joo Hang} and Cho, {Eun Kyung} and Hoffman, {Philip C.} and Orlov, {Sergey V.} and Piotr Serwatowski and Jiuzhou Wang and Foley, {Margaret A.} and Horan, {Julie D.} and Shepherd, {Frances A.}",
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TY - JOUR

T1 - Adjuvant erlotinib versus placebo in patients with stage IB-IIIA nonsmall-cell lung cancer (RADIANT)

T2 - A randomized, double-blind, Phase III trial

AU - Kelly, Karen

AU - Altorki, Nasser K.

AU - Eberhardt, Wilfried E E

AU - OBrien, Mary E R

AU - Spigel, David R.

AU - Crinò, Lucio

AU - Tsai, Chun Ming

AU - Kim, Joo Hang

AU - Cho, Eun Kyung

AU - Hoffman, Philip C.

AU - Orlov, Sergey V.

AU - Serwatowski, Piotr

AU - Wang, Jiuzhou

AU - Foley, Margaret A.

AU - Horan, Julie D.

AU - Shepherd, Frances A.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Purpose Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have proven efficacy in advanced nonsmall-cell lung cancer (NSCLC). We hypothesized that erlotinib would be efficacious in the adjuvant setting. Patients and Methods An international randomized, double-blind, placebo-controlled study was conducted in patients with completely resected IB to IIIA NSCLC whose tumors expressed EGFR protein by immunohistochemistry or EGFR amplification by fluorescence in situ hybridization. Patients were assigned 2:1 to erlotinib 150 mg once per day or placebo for 2 years. Stratification factors were stage, histology, previous adjuvant chemotherapy, smoking status, EGFR amplification status, and country. The primary end point was disease-free survival (DFS); key secondary end points were overall survival (OS) and DFS and OS in patients whose tumors had EGFR-activating mutations (EGFRm-positive). Results A total of 973 patients were randomly assigned (November 26, 2007, to July 7, 2010). There was no statistically significant difference in DFS (median, 50.5 months for erlotinib and 48.2 months for placebo; hazard ratio, 0.90; 95% CI, 0.74 to 1.10; P = .324). Among the 161 patients (16.5%) in the EGFRm-positive subgroup, DFS favored erlotinib (median, 46.4 v 28.5 months; hazard ratio, 0.61; 95% CI, 0.38 to 0.98; P = .039), but this was not statistically significant because of the hierarchical testing procedure. OS data are immature. Rash and diarrhea were common adverse events occurring in 528 (86.4%) and 319 (52.2%) patients treated with erlotinib, respectively, versus 110 (32.1%) and 54 (15.7%) patients receiving placebo. The most common grade 3 adverse events in patients treated with erlotinib were rash (22.3%) and diarrhea (6.2%). Conclusion Adjuvant erlotinib did not prolong DFS in patients with EGFR-expressing NSCLC or in the EGFRm-positive subgroup. Further evaluation of erlotinib is warranted in the EGFRmpositive subgroup.

AB - Purpose Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have proven efficacy in advanced nonsmall-cell lung cancer (NSCLC). We hypothesized that erlotinib would be efficacious in the adjuvant setting. Patients and Methods An international randomized, double-blind, placebo-controlled study was conducted in patients with completely resected IB to IIIA NSCLC whose tumors expressed EGFR protein by immunohistochemistry or EGFR amplification by fluorescence in situ hybridization. Patients were assigned 2:1 to erlotinib 150 mg once per day or placebo for 2 years. Stratification factors were stage, histology, previous adjuvant chemotherapy, smoking status, EGFR amplification status, and country. The primary end point was disease-free survival (DFS); key secondary end points were overall survival (OS) and DFS and OS in patients whose tumors had EGFR-activating mutations (EGFRm-positive). Results A total of 973 patients were randomly assigned (November 26, 2007, to July 7, 2010). There was no statistically significant difference in DFS (median, 50.5 months for erlotinib and 48.2 months for placebo; hazard ratio, 0.90; 95% CI, 0.74 to 1.10; P = .324). Among the 161 patients (16.5%) in the EGFRm-positive subgroup, DFS favored erlotinib (median, 46.4 v 28.5 months; hazard ratio, 0.61; 95% CI, 0.38 to 0.98; P = .039), but this was not statistically significant because of the hierarchical testing procedure. OS data are immature. Rash and diarrhea were common adverse events occurring in 528 (86.4%) and 319 (52.2%) patients treated with erlotinib, respectively, versus 110 (32.1%) and 54 (15.7%) patients receiving placebo. The most common grade 3 adverse events in patients treated with erlotinib were rash (22.3%) and diarrhea (6.2%). Conclusion Adjuvant erlotinib did not prolong DFS in patients with EGFR-expressing NSCLC or in the EGFRm-positive subgroup. Further evaluation of erlotinib is warranted in the EGFRmpositive subgroup.

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