Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer

RTOG 0324

George R. Blumenschein, Rebecca Paulus, Walter J. Curran, Francisco Robert, Frank Fossella, Maria Werner-Wasik, Roy S. Herbst, Philip O. Doescher, Hak Choy, Ritsuko Komaki

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Purpose: Non-small-cell lung cancer (NSCLC) commonly expresses the epidermal growth factor receptor (EGFR), which is associated with poor clinical outcome. Cetuximab is a chimerized monoclonal antibody that targets the EGFR and, in preclinical models, it demonstrates radiosensitization properties. We report a phase II trial testing the combination of cetuximab with chemoradiotherapy (CRT) in unresectable stage III NSCLC. Patients and Methods: Eligibility criteria included unresectable stage III NSCLC, Zubrod performance status ≤ 1, weight loss ≤ 5%, forced expiratory volume in 1 second ≥ 1.2 L, and adequate organ function. Patients received an initial dose of cetuximab (400 mg/m2) on day 1 of week 1 and then weekly doses of cetuximab (250 mg/m2) until completion of therapy (weeks 2 through 17). During week 2, patients started CRT (63 Gy in 35 fractions) with weekly carboplatin at area under the [concentration-time] curve (AUC) 2 and six doses of paclitaxel at 45 mg/m2 followed by carboplatin (AUC 6) and two cycles of paclitaxel (200 mg/m2) during weeks 12 through 17. Primary end points included safety and compliance of concurrent cetuximab and CRT. Results: In all, 93 patients were enrolled and 87 were evaluable. Median follow-up was 21.6 months. Response rate was 62% (n = 54), median survival was 22.7 months, and 24-month overall survival was 49.3%. Adverse events related to treatment included 20% grade 4 hematologic toxicities, 8% grade 3 esophagitis, and 7% grade 3 to 4 pneumonitis. There were five grade 5 events. Conclusion: The combination of cetuximab with CRT is feasible and shows promising activity. The median and overall survival achieved with this regimen were longer than any previously reported by the Radiation Therapy Oncology Group.

Original languageEnglish (US)
Pages (from-to)2312-2318
Number of pages7
JournalJournal of Clinical Oncology
Volume29
Issue number17
DOIs
StatePublished - Jun 10 2011

Fingerprint

Non-Small Cell Lung Carcinoma
Chemoradiotherapy
Carboplatin
Paclitaxel
Epidermal Growth Factor Receptor
Area Under Curve
Survival
Radiation Oncology
Esophagitis
Forced Expiratory Volume
Cetuximab
Weight Loss
Pneumonia
Radiotherapy
Monoclonal Antibodies
Safety
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Blumenschein, G. R., Paulus, R., Curran, W. J., Robert, F., Fossella, F., Werner-Wasik, M., ... Komaki, R. (2011). Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer: RTOG 0324. Journal of Clinical Oncology, 29(17), 2312-2318. https://doi.org/10.1200/JCO.2010.31.7875

Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer : RTOG 0324. / Blumenschein, George R.; Paulus, Rebecca; Curran, Walter J.; Robert, Francisco; Fossella, Frank; Werner-Wasik, Maria; Herbst, Roy S.; Doescher, Philip O.; Choy, Hak; Komaki, Ritsuko.

In: Journal of Clinical Oncology, Vol. 29, No. 17, 10.06.2011, p. 2312-2318.

Research output: Contribution to journalArticle

Blumenschein, GR, Paulus, R, Curran, WJ, Robert, F, Fossella, F, Werner-Wasik, M, Herbst, RS, Doescher, PO, Choy, H & Komaki, R 2011, 'Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer: RTOG 0324', Journal of Clinical Oncology, vol. 29, no. 17, pp. 2312-2318. https://doi.org/10.1200/JCO.2010.31.7875
Blumenschein, George R. ; Paulus, Rebecca ; Curran, Walter J. ; Robert, Francisco ; Fossella, Frank ; Werner-Wasik, Maria ; Herbst, Roy S. ; Doescher, Philip O. ; Choy, Hak ; Komaki, Ritsuko. / Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer : RTOG 0324. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 17. pp. 2312-2318.
@article{2da815c7b941492ead77e2cf3dc82dd1,
title = "Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer: RTOG 0324",
abstract = "Purpose: Non-small-cell lung cancer (NSCLC) commonly expresses the epidermal growth factor receptor (EGFR), which is associated with poor clinical outcome. Cetuximab is a chimerized monoclonal antibody that targets the EGFR and, in preclinical models, it demonstrates radiosensitization properties. We report a phase II trial testing the combination of cetuximab with chemoradiotherapy (CRT) in unresectable stage III NSCLC. Patients and Methods: Eligibility criteria included unresectable stage III NSCLC, Zubrod performance status ≤ 1, weight loss ≤ 5{\%}, forced expiratory volume in 1 second ≥ 1.2 L, and adequate organ function. Patients received an initial dose of cetuximab (400 mg/m2) on day 1 of week 1 and then weekly doses of cetuximab (250 mg/m2) until completion of therapy (weeks 2 through 17). During week 2, patients started CRT (63 Gy in 35 fractions) with weekly carboplatin at area under the [concentration-time] curve (AUC) 2 and six doses of paclitaxel at 45 mg/m2 followed by carboplatin (AUC 6) and two cycles of paclitaxel (200 mg/m2) during weeks 12 through 17. Primary end points included safety and compliance of concurrent cetuximab and CRT. Results: In all, 93 patients were enrolled and 87 were evaluable. Median follow-up was 21.6 months. Response rate was 62{\%} (n = 54), median survival was 22.7 months, and 24-month overall survival was 49.3{\%}. Adverse events related to treatment included 20{\%} grade 4 hematologic toxicities, 8{\%} grade 3 esophagitis, and 7{\%} grade 3 to 4 pneumonitis. There were five grade 5 events. Conclusion: The combination of cetuximab with CRT is feasible and shows promising activity. The median and overall survival achieved with this regimen were longer than any previously reported by the Radiation Therapy Oncology Group.",
author = "Blumenschein, {George R.} and Rebecca Paulus and Curran, {Walter J.} and Francisco Robert and Frank Fossella and Maria Werner-Wasik and Herbst, {Roy S.} and Doescher, {Philip O.} and Hak Choy and Ritsuko Komaki",
year = "2011",
month = "6",
day = "10",
doi = "10.1200/JCO.2010.31.7875",
language = "English (US)",
volume = "29",
pages = "2312--2318",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "17",

}

TY - JOUR

T1 - Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer

T2 - RTOG 0324

AU - Blumenschein, George R.

AU - Paulus, Rebecca

AU - Curran, Walter J.

AU - Robert, Francisco

AU - Fossella, Frank

AU - Werner-Wasik, Maria

AU - Herbst, Roy S.

AU - Doescher, Philip O.

AU - Choy, Hak

AU - Komaki, Ritsuko

PY - 2011/6/10

Y1 - 2011/6/10

N2 - Purpose: Non-small-cell lung cancer (NSCLC) commonly expresses the epidermal growth factor receptor (EGFR), which is associated with poor clinical outcome. Cetuximab is a chimerized monoclonal antibody that targets the EGFR and, in preclinical models, it demonstrates radiosensitization properties. We report a phase II trial testing the combination of cetuximab with chemoradiotherapy (CRT) in unresectable stage III NSCLC. Patients and Methods: Eligibility criteria included unresectable stage III NSCLC, Zubrod performance status ≤ 1, weight loss ≤ 5%, forced expiratory volume in 1 second ≥ 1.2 L, and adequate organ function. Patients received an initial dose of cetuximab (400 mg/m2) on day 1 of week 1 and then weekly doses of cetuximab (250 mg/m2) until completion of therapy (weeks 2 through 17). During week 2, patients started CRT (63 Gy in 35 fractions) with weekly carboplatin at area under the [concentration-time] curve (AUC) 2 and six doses of paclitaxel at 45 mg/m2 followed by carboplatin (AUC 6) and two cycles of paclitaxel (200 mg/m2) during weeks 12 through 17. Primary end points included safety and compliance of concurrent cetuximab and CRT. Results: In all, 93 patients were enrolled and 87 were evaluable. Median follow-up was 21.6 months. Response rate was 62% (n = 54), median survival was 22.7 months, and 24-month overall survival was 49.3%. Adverse events related to treatment included 20% grade 4 hematologic toxicities, 8% grade 3 esophagitis, and 7% grade 3 to 4 pneumonitis. There were five grade 5 events. Conclusion: The combination of cetuximab with CRT is feasible and shows promising activity. The median and overall survival achieved with this regimen were longer than any previously reported by the Radiation Therapy Oncology Group.

AB - Purpose: Non-small-cell lung cancer (NSCLC) commonly expresses the epidermal growth factor receptor (EGFR), which is associated with poor clinical outcome. Cetuximab is a chimerized monoclonal antibody that targets the EGFR and, in preclinical models, it demonstrates radiosensitization properties. We report a phase II trial testing the combination of cetuximab with chemoradiotherapy (CRT) in unresectable stage III NSCLC. Patients and Methods: Eligibility criteria included unresectable stage III NSCLC, Zubrod performance status ≤ 1, weight loss ≤ 5%, forced expiratory volume in 1 second ≥ 1.2 L, and adequate organ function. Patients received an initial dose of cetuximab (400 mg/m2) on day 1 of week 1 and then weekly doses of cetuximab (250 mg/m2) until completion of therapy (weeks 2 through 17). During week 2, patients started CRT (63 Gy in 35 fractions) with weekly carboplatin at area under the [concentration-time] curve (AUC) 2 and six doses of paclitaxel at 45 mg/m2 followed by carboplatin (AUC 6) and two cycles of paclitaxel (200 mg/m2) during weeks 12 through 17. Primary end points included safety and compliance of concurrent cetuximab and CRT. Results: In all, 93 patients were enrolled and 87 were evaluable. Median follow-up was 21.6 months. Response rate was 62% (n = 54), median survival was 22.7 months, and 24-month overall survival was 49.3%. Adverse events related to treatment included 20% grade 4 hematologic toxicities, 8% grade 3 esophagitis, and 7% grade 3 to 4 pneumonitis. There were five grade 5 events. Conclusion: The combination of cetuximab with CRT is feasible and shows promising activity. The median and overall survival achieved with this regimen were longer than any previously reported by the Radiation Therapy Oncology Group.

UR - http://www.scopus.com/inward/record.url?scp=79959195283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959195283&partnerID=8YFLogxK

U2 - 10.1200/JCO.2010.31.7875

DO - 10.1200/JCO.2010.31.7875

M3 - Article

VL - 29

SP - 2312

EP - 2318

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 17

ER -