Phase II selection design trial of concurrent chemotherapy and cetuximab versus chemotherapy followed by cetuximab in advanced-stage non-small-cell lung cancer: Southwest Oncology Group study S0342.

Abstract

PURPOSE:

Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation.

PATIENTS AND METHODS:

Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m(2)) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m(2) loading dose followed by 250 mg/m(2) weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel-carboplatin for four cycles followed by cetuximab.

RESULTS:

Of 242 patients enrolled, 224 were eligible and assessable for response (106 and 118 patients in the concurrent and sequential arms, respectively). With a median follow-up time of 32 months, the median overall survival was 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P = .57); 1-year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35% to 53%), respectively. Response rates and progression-free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm (15% v 5% in the sequential arm; P = .036).

CONCLUSION:

Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen.

• Authors: Roy S Herbst, Karen Kelly, Kari Chansky, Philip C Mack, Wilbur A Franklin, Fred R Hirsch, James N Atkins, Shaker R Dakhil, Kathy S Albain, Edward S Kim, Mary Redman, John J Crowley, David R Gandara
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 31 Pg. 4747-54 (Nov 01 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20921467 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Biomarkers, Tumor
• KRAS protein, human
• Proto-Oncogene Proteins
• Quinazolines
• Carboplatin
• Erlotinib Hydrochloride
• ErbB Receptors
• Proto-Oncogene Proteins p21(ras)
• ras Proteins
• Paclitaxel
• Cetuximab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Biomarkers, Tumor (genetics)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, secondary)
• Cetuximab
• Disease-Free Survival
• Drug Administration Schedule
• ErbB Receptors (antagonists & inhibitors)
• Erlotinib Hydrochloride
• Female
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Mutation
• Neoplasm Staging
• Paclitaxel (administration & dosage)
• Patient Selection
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins p21(ras)
• Quinazolines (administration & dosage)
• Research Design
• Southwestern United States
• Treatment Outcome
• ras Proteins (genetics)