Randomized, Phase III Trial of First-Line Figitumumab in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Patients With Advanced Non-Small-Cell Lung Cancer

• Published in: Journal of clinical oncology Vol. 32; no. 19; pp. 2059 - 2066
• Main Authors: LANGER, Corey J, NOVELLO, Silvia, KEUNCHIL PARK, KRZAKOWSKI, Maciej, KARP, Daniel D, MOK, Tony, BENNER, Rebecca J, SCRANTON, Judith R, OLSZANSKI, Anthony J, JASSEM, Jacek
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01.07.2014
• Subjects: Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Disease-Free Survival; Drug Administration Schedule; Female; Glycated Hemoglobin - metabolism; Humans; Insulin-Like Growth Factor I - metabolism; Kaplan-Meier Estimate; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); ORIGINAL REPORTS; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Pneumology; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum; Antineoplastic agent; Phase III trial; Lung cancer; Monoclonal antibody; non-small cell lung carcinoma; Randomization; Cancerology; Taxane derivatives; Paclitaxel; Bronchus disease; Clinical trial; Advanced stage; Antimitotic; Figitumumab; Platinum II Complexes; Human; Lung disease; Drug combination; Respiratory disease; Malignant tumor; First line treatment; Chemotherapy; Treatment; Carboplatin; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2013.54.4932

Figitumumab (CP-751,871), a fully human immunoglobulin G2 monoclonal antibody, inhibits the insulin-like growth factor 1 receptor (IGF-1R). Our multicenter, randomized, phase III study compared figitumumab plus chemotherapy with chemotherapy alone as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). Patients with stage IIIB/IV or recurrent NSCLC disease with nonadenocarcinoma histology received open-label figitumumab (20 mg/kg) plus paclitaxel (200 mg/m(2)) and carboplatin (area under the concentration-time curve, 6 mg · min/mL) or paclitaxel and carboplatin alone once every 3 weeks for up to six cycles. The primary end point was overall survival (OS). Of 681 randomly assigned patients, 671 received treatment. The study was closed early by an independent Data Safety Monitoring Committee because of futility and an increased incidence of serious adverse events (SAEs) and treatment-related deaths with figitumumab. Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively. The respective rates of all-causality SAEs were 66% and 51%; P < .01). Treatment-related grade 5 adverse events were also more common with figitumumab (5% v 1%; P < .01). Adding figitumumab to standard chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma NSCLC. Further clinical development of figitumumab is not being pursued.