Gemcitabine/platinum alone or in combination with cetuximab as first-line treatment for advanced non-small cell lung cancer (NSCLC)

Abstract

7539 Background: This randomized phase II study was conducted to evaluate the benefit of adding cetuximab, an IgG1 monoclonal antibody targeting the EGF receptor, to gemcitabine/platinum chemotherapy in patients with recurrent or metastatic NSCLC. Methods: Patients with previously untreated stage IIIB (malignant pleural effusion) or stage IV NSCLC irrespective of their EGF receptor status were eligible for this study. Patients on arm A received cetuximab (400 mg/m2 IV on day 1 followed by 250 mg/m2 weekly) combined with either cisplatin (75 mg/m2 IV q3 weeks) and gemcitabine (1,250 mg/m2 IV days 1 and 8) or carboplatin (AUC 5 IV q3 weeks) and gemcitabine (1,000 mg/m2 IV days 1 and 8). Patients on Arm B received the same chemotherapy regimen without cetuximab. The primary endpoint was tumor response rate with progression-free (PFS) and overall survival (OS) as secondary endpoints. Results: 73 women and 58 men, median age 66 years (35–88) were randomized to arm A (n=65) or arm B (n=66). Partial responses occurred in 18 (27.7%, 95% CI: 17.3–40.2) patients in arm A and 12 (18.2%, 95% CI 9.8–29.6) in arm B. Median PFS was 5.09 months for arm A (95% CI: 4.17–5.98) and 4.21 months (95% CI: 3.81–5.49) in arm B; median OS was 11.99 (95% CI: 8.80–15.20) and 9.26 months (95% CI: 7.43–11.79) respectively. The incidence of drug related infusion reactions (any grade) in arm A was 15.6% and 1.5% in arm B. Three patients in arm A had grade 3–4 cetuximab related infusion reactions. Severe acneform rash was observed in 14.1% of patients in arm A and none in arm B. Other toxicities were similar and only 18.5% of patients in arm A and 10.6% patients in arm B discontinued treatment for toxicity. Conclusions: These data confirm the previously observed benefit for the combination of cetuximab with a platinum based doublet chemotherapy regimen patients with metastatic NSCLC. The difference of 2.7 months in median OS between treatment arms seems to suggest a more substantial clinical benefit. Fully powered phase III studies addressing this question are on- going and results will become available in 2007. [Table: see text]