Phase II randomized, open-label study of cetuximab (Cet) and bevacizumab (Bev) in combination with paclitaxel (P) and carboplatin (C) in patients with stageIII/IV non-small cell lung cancer (NSCLC)

Abstract

8046^ Background: Cet, a monoclonal antibody (mAb) that specifically targets epidermal growth factor receptor (EGFR) and Bev (anti-VEGF mAb) combined with chemotherapy has resulted in superior survival compared to chemotherapy alone in some stage IV NSCLC trials. Combining both mAb's with chemotherapy might increase survival in stage IV NSCLC pts. Methods: Chemotherapy naïve advanced NSCLC patients with ECOG status <1, adequate hematologic, hepatic, and renal function received Cet (400 mg/m2 on Day 1 as initial dose and weekly thereafter at 250 mg/m2) plus Bev (15 mg/kg on Day 8 of each 3-week cycle) for 6 cycles in combination with either 6 cycles (Arm A) or 3 cycles (Arm B) of P (200 m/kg) and C (AUC=6) on Day 1 of each 3-week cycle. Patients without progressive disease (PD) after 6 cycles continued Cet until PD or other withdrawal criteria were met. Comparison of progression-free survival (PFS) for arm A vs B is the primary objective. Results: Accrual is completed. Data are available for 85 pts: 47% women, median age 65 yrs, and 88% Caucasian. Median PFS for arm A was 6.0 vs 4.2 months for arm B, hazard ratio of 0.57 for arm A relative to arm B. Objective response was Arm A=31% and B=30%. Most frequent AEs ≥Grade 3 in pts were neutropenia [9 (10.6%), A=8, B=1], fatigue [8 (9.4%), A=4, B=4], dermatitis acneiform [6 (7.1%), A=3, B=3].13 pts withdrew due to AEs (A=4, B=9), 4 were related to Cet (2 per arm). Two pts discontinued due to death (A=2, B=0) unrelated to Cet. Conclusions: Adding both mAb's to PC resulted in acceptable toxicity. The trend for superior PFS with 6 courses of PC suggests that 3 courses of PC are not optimal. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .