Cetuximab plus FOLFOX for colorectal cancer (EXPLORE): Preliminary efficacy analysis of a randomized phase III trial

Abstract

3574 Background: The EXPLORE study was designed as a randomized phase III study in patients (pts) with metastatic EGFR-positive colorectal cancer (CRC) who had received irinotecan in 1st-line. Pts were to receive either cetuximab (Erbitux) plus FOLFOX4 (5-FU, leucovorin, oxaliplatin), or FOLFOX4. The primary endpoint of the study was to be survival with secondary endpoints including response rate and time-to-progression. Although the study was designed to accrue 1100 pts, due to recent changes in clinical practice resulting in the replacement of irinotecan with oxaliplatin in the 1st-line setting, accrual to the current trial was stopped. An analysis of safety on the first 40 pts randomized to the study was reported at ASCO 2004 (Abstr# 3531). Methods: Pts with metastatic EGFR-positive CRC who had progressed on prior 1st-line irinotecan therapy with an ECOG performance status ≤ 2 received either Cetuximab 400 mg/m2 initial dose followed by 250 mg/m2 weekly dose and FOLFOX4 d1,d2 q 2 weeks (Arm A) or FOLFOX4 q 2 weeks (Arm B). Results: 102 pts were randomized from March 2003 through October 2004. Dosing information is available on 90 pts: 41 women and 49 men with a median age of 59 years (range 29–08). Forty-three pts treated on Arm A received a total of 407 cycles with a median of 8 cycles per patient (range 1–36). Forty-seven pts on Arm B received a total of 304 cycles with a median of 6 cycles per patient (range 1–20). Tumor measurements are available for 43 pts on Arm A and for 42 pts on Arm B pts. In Arm A, 9 pts had partial responses (PR), 20 pts had stable disease (SD) (including 2 unconfirmed PRs (uPR)), and 6 pts had progressive disease (PD). It was too early to report a response in an additional 8 pts. In Arm B, 4 pts had PRs, 26 had SDs (including 2 uPRs), and 9 had PDs. It was too early to determine a response in an additional 3 pts. Of the pts assessed for efficacy, 7 pts on Arm A and 5 pts on Arm B remain on study. The study is closed to accrual and final data on all pts will be presented at the meeting. Conclusions: The combination of FOLFOX4 and Cetuximab is active in pts with metastatic CRC previously treated with irinotecan. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb