Panitumumab versus cetuximab in patients with wild-type KRAS exon 2 metastatic colorectal cancer who received prior bevacizumab therapy: A combined analysis of individual patient data from ASPECCT and WJOG6510G.

Abstract

745 Background: The ASPECCT (Price T, et al. Eur J Cancer 2016) and WJOG6510G (Sugimoto N, et al. ASCO-GI 2017) trials demonstrated noninferiority of panitumumab (Pmab), compared with cetuximab (Cmab), regarding the overall survival (OS) for chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC). However, the subgroup analyses of both trials revealed a longer survival with Pmab than Cmab in patients who previously received bevacizumab (Bev). We performed a combined analysis of both trials using individual patient data. Methods: In both trials, patients with wild-type KRAS exon 2 mCRC who progressed on or were intolerant to CPT-11- or L-OHP-based chemotherapy were randomized to receive Pmab or Cmab monotherapy (ASPECCT) or in combination with CPT-11 (WJOG). The patient subgroup with prior Bev was eligible for enrollment in this analysis. Results: In the combined data of 374 patients, 185 patients were enrolled in the Pmab arm (ASPECCT, 126; WJOG, 59) and 189 patients in the Cmab arm (ASPECCT, 132; WJOG, 57). The patient characteristics were well-balanced in both arms. Of the 374 patients, 341 (91%) and 369 (99%) had the OS and progression-free survival (PFS) events, respectively. The median OS was 12.8 months in the Pmab arm and 10.1 months in the Cmab arm ( P = 0.0031; the log-rank test stratified by trial). The hazard ratio (HR) for OS was 0.72 (95% confidence interval [CI], 0.58–0.90). The median PFS in the Pmab and Cmab arms were 4.7 and 4.1 months, respectively (P = 0.0207). HR for PFS was 0.79 (95% CI: 0.64–0.97). Response rates in the Pmab and Cmab arms were 23% and 16%, respectively (P = 0.114). Although the incidence of skin toxicities was similar, the infusion reaction was observed more in the Cmab arm (any grade, 1.1% vs 8.6%), whereas hypomagnesemia was noted more in the Pmab arm (48% vs 33%). Conclusions: This combined analysis demonstrated that Pmab significantly prolonged OS and PFS compared with Cmab, raising the potential that Pmab is the more reliable anti-EGFR option for patients with wild-type KRAS exon 2 metastatic colorectal cancer who previously received Bev.