A randomized multicenter phase III study of cetuximab (Erbitux(R)) in combination with Taxane/Carboplatin versus Taxane/Carboplatin alone as first-line treatment for patients with advanced/metastatic Non-small cell lung cancer (NSCLC): B3-03

Background:

Cetuximab (Erbitux®) is a chimeric monoclonal IgG1 antibody targeting the epidermal growth factor receptor (EGFR) thereby blocking ligand-receptor interaction, promoting receptor internalization, cell cycle arrest and apoptosis. Several phase II studies with cetuximab in combination with platinum based chemotherapy have shown encouraging anti-tumor activity in patients with advanced/metastatic NSCLC. This randomized phase III study was conducted to determine the efficacy of adding cetuximab to taxane/platinum chemotherapy in patients with recurrent or metastatic NSCLC in a randomized controlled setting.

Methods:

Patients with previously untreated stage IIIB (malignant pleural effusion) or stage IV NSCLC 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 paclitaxel (225 mg/m² IV q3 weeks) or docetaxel (75mg mg/m² IV q3 weeks) and carboplatin (AUC 6 IV q3 weeks). Patients on Arm B received the same chemotherapy regimen but without cetuximab. The choice of taxane was at the discretion of the investigator but had to be made before randomization since on-study taxane (paclitaxel or docetaxel), ECOG PS (0 vs. 1) and site were part of the stratification scheme. The primary endpoint was progression-free-survival (PFS) as determined by an Independent Radiology Review Committee. In order to have 90% power to detect a hazard ratio of 0.75 of the combination arm over the control arm 510 progression events were required. Secondary endpoints included response rate, time to response, duration of response, disease control rate, quality of life and overall survival (OS).

Results and Conclusions:

From December 2004 until October 2006 676 patients were randomized at 97 centers in the US: 58.6% men, 41.4 % women with a median age of 65 years (range 34-87). Data on the primary and secondary objectives along with unblinded safety data will be presented at the meeting.