The ASPECCT (Price T, et al. Eur J Cancer 2016) and WJOG6510G (Sugimoto N, et al. ASCO-GI 2017) trials demonstrated the similar efficacy of panitumumab (Pmab) and cetuximab (Cmab) for chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC). The post-hoc subgroup analyses of both trials demonstrated a longer survival with Pmab than Cmab in patients who previously received bevacizumab (Bev). In this individual patient data meta-analysis with updated follow-up, we aim to provide more precise estimates of treatment effects considering other prognostic factors.
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.
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 between both arms except for higher baseline CEA levels for the patients in Pmab arm. In univariate analysis, ECOG PS, number of metastatic sites, baseline CEA and regimen were associated with OS. 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). Even in multivariate analysis of OS, the regimen was an independent prognostic factor of OS (adjusted HR 0.69, 95% CI 0.54-0.87, p = 0.0013).
This combined analysis demonstrated that Pmab significantly prolonged OS and PFS compared with Cmab in patients previously receiving Bev. The superiority of Pmab remained unchanged after adjusting for other prognostic factors. Underlying biological mechanisms should be investigated.
Clinical trial identification
Legal entity responsible for the study
WJOG and Amgen.
Has not received any funding.
H. Taniguchi: Grants and personal fees: Takeda; Personal fees: Chugai, Taiho outside the submitted work. T. Yamanaka: Grants and personal fees: Takeda, during the conduct of the study. K. Yamazaki: Personal fees: Sanofi K.K., Chugai Pharmaceutical Co., Ltd, Eli Lilly Japan K.K, Merck Serono Co., Ltd., Yakult Honsya Co., Ltd, Bayer Yakuhin, Ltd, Taiho Pharmaceutical Co., Ltd, Sanofi K. K, Takeda Pharmaceutical Co., Ltd, Bristol-Myers Squibb K. K, outside the submitted work. K. Muro: Personal fees: Takeda and Merck Serono, during the conduct of the study. M. Peeters: Membership on an advisory board, Corporate-sponsored research, Honoraria: Amgen. T.J. Price: Grants: Amgen, during the conduct of the study. All other authors have declared no conflicts of interest.