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)

• 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
• Journal Title: Cancer
• Volume: Volume 121, Number 13
• Publisher: Wiley | 2015-07-01, Pages 2253-2261
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/cncr.29308
• Subjects: Health Sciences, Oncology; Health Sciences, Pharmacology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; carboplatin; cetuximab; cixutumumab; non-small cell lung cancer; paclitaxel; GROWTH-FACTOR-I; RECEPTOR MONOCLONAL-ANTIBODY; GENE COPY NUMBER; III TRIAL; BINDING PROTEIN-3; EGFR MUTATIONS; OPEN-LABEL; CHEMOTHERAPY; ADENOCARCINOMA; SENSITIVITY

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.