Langer, Corey J; Novello, Silvia; Park, Keunchil; Krzakowski, Maciej; Karp, Daniel D; Mok, Tony; Benner, Rebecca J; Scranton, Judith R; Olszanski, Anthony J; Jassem, Jacek
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
2014Jul ; 32 ( 19 ) :2059-66.
PMID : 24888810
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Langer, Corey J -
Novello, Silvia -
Park, Keunchil -
Krzakowski, Maciej -
Karp, Daniel D -
Mok, Tony -
Benner, Rebecca J -
Scranton, Judith R -
Olszanski, Anthony J -
Jassem, Jacek -
ABSTRACT
PURPOSE: 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 AND
METHODS: 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).
RESULTS: 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). CONCLUSION: Adding figitumumab to standard chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma NSCLC. Further clinical development of figitumumab is not being pursued. CI - ??2014 by American Society of Clinical Oncology.
Adult; Aged; Antibodies, Monoclonal/administration & dosage/adverse effects; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use; Carboplatin/administration & dosage/adverse effects; Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism/pathology; Disease-Free Survival; Drug Administration Schedule; Female; Hemoglobin A, Glycosylated/metabolism; Humans; Insulin-Like Growth Factor I/metabolism; Kaplan-Meier Estimate; Lung Neoplasms/*drug therapy/metabolism/pathology; Male; Middle Aged; Paclitaxel/administration & dosage/adverse effects; Treatment Outcome
MESH
Adult, Aged, Antibodies, Monoclonal/administration & dosage/adverse effects, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Carboplatin/administration & dosage/adverse effects, Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism/pathology, Disease-Free Survival, Drug Administration Schedule, Female, Hemoglobin A, Glycosylated/metabolism, Humans, Insulin-Like Growth Factor I/metabolism, Kaplan-Meier Estimate, Lung Neoplasms/*drug therapy/metabolism/pathology, Male, Middle Aged, Paclitaxel/administration & dosage/adverse effects, Treatment Outcome
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