All-RAS-Mutation Testing for Anti-EGFR Therapy

David H. Ilson, MD, PhD reviewing Van Cutsem E et al. J Clin Oncol 2015 Mar 1.

Patients with RAS wild-type colorectal cancer benefited from adding cetuximab to chemotherapy.

Prior studies have shown that combining the epidermal growth factor receptor (EGFR)-targeted agents cetuximab and panitumumab with chemotherapy improved outcomes in patients with RAS wild-type metastatic colorectal cancer (mCRC). Investigators now report updated results of the CRYSTAL study (J Clin Oncol 2011; 29:2011), an industry-sponsored, international phase III trial comparing fluorouracil, leucovorin, and irinotecan (FOLFIRI) chemotherapy with or without cetuximab in patients with KRAS wild-type mCRC. In the current study, the authors expanded the analysis to test for other RAS mutations, including KRAS mutations in other exons and NRAS mutations.

Among the 666 CRYSTAL patients with KRAS exon 2 wild-type tumors, 430 (65%) were evaluable for further RAS-mutation status. Of these patients, 63 (15%) had other RAS mutations. In RAS wild-type patients, the addition of cetuximab to FOLFIRI improved progression-free survival (PFS; the primary endpoint) and overall survival (OS; hazard ratios, 0.56 and 0.69, respectively). No PFS or OS benefit was seen with cetuximab for patients with any RAS mutation or for those in the expanded RAS mutation category.

Citation(s):

Van Cutsem E et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol 2015 Mar 1; 33:692.