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.

Trial registration: ClinicalTrials.gov NCT00596830.

Fig 1.

CONSORT diagram. (*) Patient analyzed in control arm for safety. AE, adverse events; IND, investigational new drug.

Fig 2.

Kaplan-Meier estimates of (A) overall survival (OS) and (B) progression-free survival (PFS) in the randomly assigned population. HR, hazard ratio.

Fig 3.

Forest plot of overall survival by selected baseline characteristics. ECOG PS, Eastern Cooperative Oncology Group performance status; HbA1_c, glycosylated hemoglobin; HR, hazard ratio.

Fig A1.

Kaplan-Meier estimates of overall survival (OS) in patients with (A) total baseline insulin-like growth factor 1 (IGF-1) less than 120 ng/mL or (B) total baseline IGF-1 ≥ 120 ng/mL. HR, hazard ratio.