Prognostic and predictive value of epidermal growth factor receptor tyrosine kinase domain mutation status and gene copy number for adjuvant chemotherapy in non-small cell lung cancer

Ming Sound Tsao, Akira Sakurada, Keyue Ding, Sarit Aviel-Ronen, Olga Ludkovski, Ni Liu, Aurélie Le Maître, David Gandara, David H. Johnson, James R. Rigas, Lesley Seymour, Frances A. Shepherd

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Abstract

PURPOSE: Patients with non-small cell lung carcinoma with epidermal growth factor receptor (EGFR) mutations may have a more favorable prognosis and greater response to chemotherapy. The effect of EGFR mutation and gene copy on patients with early-stage non-small cell lung carcinoma receiving adjuvant chemotherapy has not been reported. PATIENTS AND METHODS: Tumor samples from NCIC Clinical Trials Group JBR.10, an adjuvant trial of vinorelbine/cisplatin adjuvant chemotherapy [ACT] versus observation (OBS), were analyzed for EGFR mutation by multiple sensitive methods and copy number by fluorescent in situ hybridization. Their prognostic and predictive roles were explored in correlation with survival. RESULTS: Mutation results were available in 221 OBS and 215 ACT and fluorescent in situ hybridization results in 159 OBS and 163 ACT patients. Mutations were identified in 43 (27 OBS and 16 ACT) patients (36 sensitizing exon 19 deletions or L858R mutations). Compared with wild-type, sensitizing mutations were not significantly prognostic in OBS patients (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.38-1.63, p = 0.53). Although the presence of sensitizing mutations resulted in relatively greater benefit in ACT patients (HR: 0.44, 95% CI: 0.11-1.70, p = 0.22) compared with wild-type patients (HR: 0.78, 95% CI: 0.58-1.06, p = 0.12), this quantitative difference was not significant (interaction p = 0.50). Similarly, high EGFR copy was neither significantly prognostic nor predictive, although quantitatively it was associated with greater benefit from ACT. CONCLUSIONS: Trends toward longer survival and a greater benefit from chemotherapy were observed in patients with exon 19/21 mutations and high EGFR copy, although the differences were not statistically significant. The interpretation of the results was limited by the low EGFR mutation rate in this study of mainly white patients.

Original languageEnglish (US)
Pages (from-to)139-147
Number of pages9
JournalJournal of Thoracic Oncology
Volume6
Issue number1
DOIs
StatePublished - Jan 2011

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Gene Dosage
Adjuvant Chemotherapy
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Mutation
Observation
Confidence Intervals
Fluorescence In Situ Hybridization
Exons
erbB-1 Genes
Drug Therapy
Survival
Mutation Rate
Cisplatin
Clinical Trials

Keywords

  • Biomarker
  • Clinical trial
  • Correlative science
  • FISH
  • Predictive marker
  • Prognostic marker
  • Sequencing

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Prognostic and predictive value of epidermal growth factor receptor tyrosine kinase domain mutation status and gene copy number for adjuvant chemotherapy in non-small cell lung cancer. / Tsao, Ming Sound; Sakurada, Akira; Ding, Keyue; Aviel-Ronen, Sarit; Ludkovski, Olga; Liu, Ni; Maître, Aurélie Le; Gandara, David; Johnson, David H.; Rigas, James R.; Seymour, Lesley; Shepherd, Frances A.

In: Journal of Thoracic Oncology, Vol. 6, No. 1, 01.2011, p. 139-147.

Research output: Contribution to journalArticle

Tsao, Ming Sound ; Sakurada, Akira ; Ding, Keyue ; Aviel-Ronen, Sarit ; Ludkovski, Olga ; Liu, Ni ; Maître, Aurélie Le ; Gandara, David ; Johnson, David H. ; Rigas, James R. ; Seymour, Lesley ; Shepherd, Frances A. / Prognostic and predictive value of epidermal growth factor receptor tyrosine kinase domain mutation status and gene copy number for adjuvant chemotherapy in non-small cell lung cancer. In: Journal of Thoracic Oncology. 2011 ; Vol. 6, No. 1. pp. 139-147.
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AU - Sakurada, Akira

AU - Ding, Keyue

AU - Aviel-Ronen, Sarit

AU - Ludkovski, Olga

AU - Liu, Ni

AU - Maître, Aurélie Le

AU - Gandara, David

AU - Johnson, David H.

AU - Rigas, James R.

AU - Seymour, Lesley

AU - Shepherd, Frances A.

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N2 - PURPOSE: Patients with non-small cell lung carcinoma with epidermal growth factor receptor (EGFR) mutations may have a more favorable prognosis and greater response to chemotherapy. The effect of EGFR mutation and gene copy on patients with early-stage non-small cell lung carcinoma receiving adjuvant chemotherapy has not been reported. PATIENTS AND METHODS: Tumor samples from NCIC Clinical Trials Group JBR.10, an adjuvant trial of vinorelbine/cisplatin adjuvant chemotherapy [ACT] versus observation (OBS), were analyzed for EGFR mutation by multiple sensitive methods and copy number by fluorescent in situ hybridization. Their prognostic and predictive roles were explored in correlation with survival. RESULTS: Mutation results were available in 221 OBS and 215 ACT and fluorescent in situ hybridization results in 159 OBS and 163 ACT patients. Mutations were identified in 43 (27 OBS and 16 ACT) patients (36 sensitizing exon 19 deletions or L858R mutations). Compared with wild-type, sensitizing mutations were not significantly prognostic in OBS patients (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.38-1.63, p = 0.53). Although the presence of sensitizing mutations resulted in relatively greater benefit in ACT patients (HR: 0.44, 95% CI: 0.11-1.70, p = 0.22) compared with wild-type patients (HR: 0.78, 95% CI: 0.58-1.06, p = 0.12), this quantitative difference was not significant (interaction p = 0.50). Similarly, high EGFR copy was neither significantly prognostic nor predictive, although quantitatively it was associated with greater benefit from ACT. CONCLUSIONS: Trends toward longer survival and a greater benefit from chemotherapy were observed in patients with exon 19/21 mutations and high EGFR copy, although the differences were not statistically significant. The interpretation of the results was limited by the low EGFR mutation rate in this study of mainly white patients.

AB - PURPOSE: Patients with non-small cell lung carcinoma with epidermal growth factor receptor (EGFR) mutations may have a more favorable prognosis and greater response to chemotherapy. The effect of EGFR mutation and gene copy on patients with early-stage non-small cell lung carcinoma receiving adjuvant chemotherapy has not been reported. PATIENTS AND METHODS: Tumor samples from NCIC Clinical Trials Group JBR.10, an adjuvant trial of vinorelbine/cisplatin adjuvant chemotherapy [ACT] versus observation (OBS), were analyzed for EGFR mutation by multiple sensitive methods and copy number by fluorescent in situ hybridization. Their prognostic and predictive roles were explored in correlation with survival. RESULTS: Mutation results were available in 221 OBS and 215 ACT and fluorescent in situ hybridization results in 159 OBS and 163 ACT patients. Mutations were identified in 43 (27 OBS and 16 ACT) patients (36 sensitizing exon 19 deletions or L858R mutations). Compared with wild-type, sensitizing mutations were not significantly prognostic in OBS patients (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.38-1.63, p = 0.53). Although the presence of sensitizing mutations resulted in relatively greater benefit in ACT patients (HR: 0.44, 95% CI: 0.11-1.70, p = 0.22) compared with wild-type patients (HR: 0.78, 95% CI: 0.58-1.06, p = 0.12), this quantitative difference was not significant (interaction p = 0.50). Similarly, high EGFR copy was neither significantly prognostic nor predictive, although quantitatively it was associated with greater benefit from ACT. CONCLUSIONS: Trends toward longer survival and a greater benefit from chemotherapy were observed in patients with exon 19/21 mutations and high EGFR copy, although the differences were not statistically significant. The interpretation of the results was limited by the low EGFR mutation rate in this study of mainly white patients.

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