Randomized phase II study of panitumumab (Pmab) + irinotecan (CPT-11) versus cetuximab (Cmab) + CPT-11 in patients (pts) with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) after fluoropyrimidine (FU), CPT-11, and oxaliplatin (L-OHP) failure: WJOG6510G.

Abstract

661 Background: Continuation of CPT-11 in combination with Cmab after CPT-11 failure has a survival benefit over Cmab alone. However, it is not clear whether CPT-11 with Pmab shows similar benefits. Methods: Pts with KRAS WT mCRC previously treated with FU-, L-OHP-, and CPT-11- based chemotherapies were randomized 1:1 to either Cmab + CPT-11(Cmab arm), or Pmab + CPT-11(Pmab arm). Primary objective was progression free survival (PFS), with an expected hazard ratio (HR) of 1.0 with non-inferiority margin of 1.3 (80% CI) using cox proportional hazards model. Median PFS with both arms were assumed to be 6.0 months. Secondary objectives were overall survival (OS), response rate (RR), disease control rate (DCR), and safety. Results: From December 2011 to September 2014, 121 pts were enrolled from 31 sites in Japan. Because 1 patient declined before treatment, totally, 120 (Cmab arm: 59, Pmab arm 61) pts were eligible for efficacy analysis. Baseline characteristics were well balanced between the two arms. 116 pts (96.7 %) were previously treated with bevacizumab. Efficacy results are shown in the table. The common grade 3 or 4 adverse events in Cmab/Pmab arm were leukopenia 19.0/3.3%, neutropenia 27.6/8.3%, hypomagnesaemia 6.9/16.7%, and rash 5.2/13.3 %, respectively. Conclusions: Non-inferiority of Pmab to Cmab in combination with CPT-11 was suggested for patients with KRAS WT mCRC previously treated with FU-, L-OHP-, and CPT-11- based chemotherapies, associated with favorable PFS and OS. Clinical trial information: UMIN000006643. [Table: see text]