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]

Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced‐stage nonsmall cell lung cancer

“…A randomized phase 2 study of cisplatin and vinorelbine with or without cetuximab demonstrated higher response rates and overall survival in favor of cetuximab‐based therapy 18. Another randomized study that compared treatment with platinum/gemcitabine with or without cetuximab also demonstrated a higher response rate and progression‐free survival with the addition of cetuximab 23…”

EGFR Inhibitors as First-Line Therapy in Advanced Non-small Cell Lung Cancer

“…A randomized phase II trial of gemcitabine/platinum with or without cetuximab as first-line treatment for advanced NSCLC was recently reported. 20 Trends suggesting benefit were observed with higher response rates (28% versus 18%), PFS (5.1 month versus 4.2 months), and OS (12.0 months versus 9.3 months) in the cetuximab arm. A randomized multicenter phase III study of first-line taxane/carboplatin with or without cetuximab enrolled 676 advanced NSCLC patients at 97 U.S. centers.…”

Implications of key trials in advanced nonsmall cell lung cancer

“…In this regard, adding cetuximab to cisplatin/vinorelbine enhanced response rates (35% vs 28%) and prolonged PFS (5.0 vs 4.6 months) compared with chemotherapy alone in a randomized phase 2 study of 86 patients with previously untreated advanced NSCLC 29. Comparable results were obtained in another randomized phase 2 study when cetuximab was added to gemcitabine/platinum 30…”