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)

• Type of Material: Article
• Authors: Nasser H. Hanna, Indiana University; Suzanne E. Dahlberg, Dana-Farber Cancer Institute; Jill Kolesar, University of Wisconsin; Charu Aggarwal, University of Pennsylvania; Fred R. Hirsch, University of Colorado; Suresh Ramalingam, Emory University; Joan H. Schiller, University of Texas Southwestern Medical Center
• Language: English
• Date: 2015-07-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 American Cancer Society.
• Final Published Version (URL): http://dx.doi.org/10.1002/cncr.29308
• Title of Journal or Parent Work: Cancer
• ISSN: 0008-543X
• Volume: 121
• Issue: 13
• Start Page: 2253
• End Page: 2261
• Grant/Funding Information: This study was conducted by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA180820, CA180794, CA49883, CA180795, CA21076, CA180799, CA15488, CA180864, CA180834, CA180870, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services.
• Keywords: Life Sciences & Biomedicine; cixutumumab; GENE COPY NUMBER; CHEMOTHERAPY; carboplatin; GROWTH-FACTOR-I; BINDING PROTEIN-3; III TRIAL; OPEN-LABEL; Oncology; non-small cell lung cancer; RECEPTOR MONOCLONAL-ANTIBODY; paclitaxel; SENSITIVITY; EGFR MUTATIONS; Science & Technology; ADENOCARCINOMA; cetuximab
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Oncology

Abstract

Background: Pre-clinical evidence supports the clinical investigation of inhibitors to the insulin-like growth factor receptor (IGFR) and the epidermal growth factor receptor (EGFR) alone and in combination in patients with NSCLC. Patients and Methods: Patients with chemotherapy-naïve, advanced NSCLC and an ECOG performance status (PS) 0/1 were eligible. Patients were randomized to receive: carboplatin AUC 6 iv + paclitaxel 200 mg/m2 iv on day 1 every 3 weeks combined with either cetuximab (CET) iv weekly (arm A), cixutumumab (CIX) iv every 2 weeks (arm B), or both (arm C). Patients with non-progressive disease (PD) after 12 weeks of therapy were permitted to continue on maintenance antibody therapy until PD. The primary endpoint was progression-free survival (PFS). The design required 180 eligible patients and had an 88% power to detect a 60% increase in median PFS for either comparison (arm A vs C or arm B vs C) using the log-rank test. Results: From 9/09 until 12/10, 140 patients were accrued. The study was closed to accrual early because of excessive number of grade 5 events reported on arms A and C. Thirteen patients died during treatment (A=6; B=2; C=5), including 9 within approximately 1 month of starting therapy. The estimated median PFS for arms A/B/C were similar at 3.4, 4.2, and 4 months, respectively. Conclusions: Based upon the apparent lack of efficacy and excessive premature deaths, this study does not support the continued investigation of carboplatin + paclitaxel + CIX alone or in combination with CET in patients with advanced NSCLC.