Three-arm, randomized, phase 2 study of carboplatin and paclitaxel in combination with cetuximab, cixutumumab, or both for advanced non-small cell lung cancer (NSCLC) patients who will not receive bevacizumab-based therapy: An Eastern Cooperative Oncology Group (ECOG) study (E4508).
BACKGROUND
Preclinical evidence supports the clinical investigation of inhibitors to the insulin-like growth factor receptor (IGFR) and the epidermal growth factor receptor (EGFR) either alone or in combination as treatment for patients with non-small cell lung cancer (NSCLC).


METHODS
Patients with chemotherapy-naïve, advanced NSCLC who had an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomized to receive carboplatin intravenously at an area under the plasma drug concentration-time curve of 6.0 plus paclitaxel 200 mg/m(2) intravenously on day 1 every 3 weeks combined with either intravenous cetuximab weekly (arm A), intravenous cixutumumab every 2 weeks (arm B), or both (arm C). Patients who had nonprogessing disease after 12 weeks of therapy were permitted to continue on maintenance antibody therapy until they developed progressive disease. The primary endpoint was progression-free survival (PFS). The study design required 180 eligible patients and had 88% power to detect a 60% increase in median PFS for either comparison (arm A vs arm C or arm B vs arm C) using the log-rank test.


RESULTS
From September 2009 to December 2010, 140 patients were accrued. The study was closed to accrual early because of an excessive number of grade 5 events reported on arms A and C. Thirteen patients died during treatment (6 patients on arm A, 2 patients on arm B, and 5 patients on arm C), including 9 within approximately 1 month of starting therapy. The estimated median PFS for arms A, B, and C were similar at 3.4 months, 4.2 months, and 4 months, respectively.


CONCLUSIONS
On the basis of the apparent lack of efficacy and excessive premature deaths, the current results do not support the continued investigation of carboplatin, paclitaxel, and cixutumumab either alone or in combination with cetuximab for patients with advanced NSCLC.
Indiana University Health Simon Cancer Center, Indianapolis, Indiana.
Nasser H
NH
Hanna
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Suzanne E
SE
Dahlberg
School of Pharmacy, University of Wisconsin, Madison, Wisconsin.
Jill M
JM
Kolesar
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
Charu
C
Aggarwal
School of Medicine, Division of Medical Oncology, University of Colorado, Denver, Colorado.
Fred R
FR
Hirsch
Winship Cancer Institute of Emory University, Atlanta, Georgia.
Suresh S
SS
Ramalingam
Hematology/Oncology Division, University of Texas Southwestern Medical Center, Dallas, Texas.
Joan H
JH
Schiller
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D000068818:Cetuximab / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C557414:cixutumumab; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel; D000068818:Cetuximab
carboplatin; cetuximab; cixutumumab; non-small cell lung cancer; paclitaxel