A multicenter phase II study of cetuximab in combination with chest radiotherapy and consolidation chemotherapy in patients with stage III non-small cell lung cancer

S. S. Ramalingam, A. Kotsakis, A. A. Tarhini, D. E. Heron, R. Smith, D. Friedland, D. P. Petro, L. E. Raez, J. R. Brahmer, J. S. Greenberger, S. Dacic, P. Hershberger, R. J. Landreneau, J. D. Luketich, C. P. Belani, A. Argiris

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Abstract

Background: Cetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC). Methods: Patients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5. Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63. Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH). Results: Forty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes. Conclusions: The addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.

Original languageEnglish (US)
Pages (from-to)416-421
Number of pages6
JournalLung Cancer
Volume81
Issue number3
DOIs
StatePublished - Sep 1 2013

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Consolidation Chemotherapy
Non-Small Cell Lung Carcinoma
Radiotherapy
Thorax
Esophagitis
Fluorescence In Situ Hybridization
erbB-1 Genes
Gene Dosage
Survival
Carboplatin
Paclitaxel
Exanthema
Combination Drug Therapy
Neutropenia
Disease-Free Survival
Cetuximab
Neoplasms
Pneumonia
Therapeutics
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Ramalingam, S. S. ; Kotsakis, A. ; Tarhini, A. A. ; Heron, D. E. ; Smith, R. ; Friedland, D. ; Petro, D. P. ; Raez, L. E. ; Brahmer, J. R. ; Greenberger, J. S. ; Dacic, S. ; Hershberger, P. ; Landreneau, R. J. ; Luketich, J. D. ; Belani, C. P. ; Argiris, A. / A multicenter phase II study of cetuximab in combination with chest radiotherapy and consolidation chemotherapy in patients with stage III non-small cell lung cancer. In: Lung Cancer. 2013 ; Vol. 81, No. 3. pp. 416-421.
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abstract = "Background: Cetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC). Methods: Patients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5. Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63. Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH). Results: Forty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67{\%}. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69{\%}) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes. Conclusions: The addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.",
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Ramalingam, SS, Kotsakis, A, Tarhini, AA, Heron, DE, Smith, R, Friedland, D, Petro, DP, Raez, LE, Brahmer, JR, Greenberger, JS, Dacic, S, Hershberger, P, Landreneau, RJ, Luketich, JD, Belani, CP & Argiris, A 2013, 'A multicenter phase II study of cetuximab in combination with chest radiotherapy and consolidation chemotherapy in patients with stage III non-small cell lung cancer', Lung Cancer, vol. 81, no. 3, pp. 416-421. https://doi.org/10.1016/j.lungcan.2013.06.002

A multicenter phase II study of cetuximab in combination with chest radiotherapy and consolidation chemotherapy in patients with stage III non-small cell lung cancer. / Ramalingam, S. S.; Kotsakis, A.; Tarhini, A. A.; Heron, D. E.; Smith, R.; Friedland, D.; Petro, D. P.; Raez, L. E.; Brahmer, J. R.; Greenberger, J. S.; Dacic, S.; Hershberger, P.; Landreneau, R. J.; Luketich, J. D.; Belani, C. P.; Argiris, A.

In: Lung Cancer, Vol. 81, No. 3, 01.09.2013, p. 416-421.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A multicenter phase II study of cetuximab in combination with chest radiotherapy and consolidation chemotherapy in patients with stage III non-small cell lung cancer

AU - Ramalingam, S. S.

AU - Kotsakis, A.

AU - Tarhini, A. A.

AU - Heron, D. E.

AU - Smith, R.

AU - Friedland, D.

AU - Petro, D. P.

AU - Raez, L. E.

AU - Brahmer, J. R.

AU - Greenberger, J. S.

AU - Dacic, S.

AU - Hershberger, P.

AU - Landreneau, R. J.

AU - Luketich, J. D.

AU - Belani, C. P.

AU - Argiris, A.

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Background: Cetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC). Methods: Patients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5. Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63. Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH). Results: Forty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes. Conclusions: The addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.

AB - Background: Cetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC). Methods: Patients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5. Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63. Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH). Results: Forty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes. Conclusions: The addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.

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