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.

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.

• Authors: Corey J Langer, Silvia Novello, Keunchil Park, Maciej Krzakowski, Daniel D Karp, Tony Mok, Rebecca J Benner, Judith R Scranton, Anthony J Olszanski, Jacek Jassem
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 19 Pg. 2059-66 (Jul 01 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 24888810 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Antibodies, Monoclonal
• Glycated Hemoglobin A
• hemoglobin A1c protein, human
• Insulin-Like Growth Factor I
• Carboplatin
• Paclitaxel
• figitumumab

Topics

• 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
• Glycated Hemoglobin (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