Extended RAS Analysis of the Phase III EPIC Trial: Irinotecan + Cetuximab Versus Irinotecan as Second-Line Treatment for Patients with Metastatic Colorectal Cancer

The oncologist

article

Alberto Sobrero¹  Heinz-Josef Lenz²  Cathy Eng³  Werner Scheithauer⁴  Gary Middleton⁵  Wenfeng Chen⁶  Regina Esser⁷  Johannes Nippgen⁶  Howard Burris⁸ 

[1] IRCCS San Martino Policlínico;Keck School of Medicine of the University of Southern California;University of Texas MD Anderson Cancer Center;Medical University of Vienna;College of Medical and Dental Sciences, University of Birmingham, United Kingdom;Ltd.;Merck KGaA;Tennessee Oncology Sarah Cannon Research Institute

关键词: Cetuximab;    Irinotecan;    Metastatic colorectal cancer;    EPIC;    RAS;   

DOI  :  10.1002/onco.13591

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background The multicenter, open-label, randomized, phase III EPIC study (EMR 062202-025) investigated cetuximab plus irinotecan versus irinotecan in patients with epidermal growth factor receptor–detectable metastatic colorectal cancer (mCRC) that progressed on first-line fluoropyrimidine- and oxaliplatin-based chemotherapy; we report the outcomes of patients with RAS- wild-type (wt) disease. Materials and Methods Available DNA samples from RAS -unselected patients ( n = 1,164 of 1,298 [89.7%]) were reanalyzed for RAS mutations using beads, emulsion, amplification, and magnetics. Baseline characteristics, efficacy, safety, and poststudy therapy were assessed. RAS -wt status was defined as a mutated RAS allele frequency of ≤5%, with all relevant alleles being analyzable. Results Baseline characteristics were comparable between the groups ( n = 452 patients with RAS- wt mCRC; cetuximab plus irinotecan n = 231, irinotecan n = 221) and between the RAS -wt and RAS -unselected populations. In the cetuximab plus irinotecan versus irinotecan arms, median overall survival was 12.3 versus 12.0 months, median progression-free survival (PFS) was 5.4 versus 2.6 months, and objective response rate (ORR) was 29.4% versus 5.0%, respectively. Quality of life (QoL) was improved in the cetuximab plus irinotecan arm. Serious adverse events occurred in 45.4% (cetuximab plus irinotecan) and 42.4% (irinotecan) of patients. In total, 47.1% of patients in the irinotecan arm received subsequent cetuximab therapy. Conclusion PFS, ORR, and QoL were improved with cetuximab plus irinotecan as a second-line treatment in patients with RAS- wt mCRC, confirming that cetuximab-based therapy is suitable in this population. Almost half of patients in the irinotecan arm received poststudy cetuximab, masking a potential overall survival benefit of cetuximab addition. Implications for Practice Cetuximab is approved for the treatment of RAS –wild-type metastatic colorectal cancer (mCRC). In this retrospective analysis of the phase III EPIC study (cetuximab plus irinotecan vs. irinotecan alone as second-line treatment in patients with RAS -unselected mCRC), the subgroup of patients with RAS –wild-type mCRC who received cetuximab plus irinotecan had improved progression-free survival, objective response rate, and quality of life compared with the RAS -unselected population. These findings suggest that cetuximab-based therapy is a suitable second-line treatment for patients with RAS –wild-type mCRC.

【 授权许可】

CC BY|CC BY-NC