Clinical benefit of high-sensitivity KRAS mutation testing in metastatic colorectal cancer treated with anti-EGFR antibody therapy

Oncology
Tetsuo KimuraTetsuji Takayama

Abstract

We compared high-sensitivity KRAS mutation testing with direct sequencing for predicting the efficacy of antiepidermal growth factor receptor antibodies in patients with metastatic colorectal cancer (mCRC). We analyzed the KRAS status in 61 tumors from cetuximab-treated mCRC patients by both direct sequencing and a high-sensitivity method: 2-step PCR restriction fragmentation length polymorphism (RFLP). Therapeutic effects in each mutational status were evaluated. The incidences of KRAS mutations determined by direct sequencing and 2-step PCR RFLP were 34.4 and 52.5%, respectively (p = 0.02). Patients were categorized into 3 groups [W/W, wild-type by both methods (n = 29); W/M, wild-type by direct sequencing, detected mutation by 2-step PCR RFLP (n = 11); M/M, mutant-type by both methods (n = 21)]. The response rate for cetuximab in the W/M group (0%) was the same as that in the M/M group, and was significantly lower than in the W/W group (41.4%) (p < 0.001). Progression-free survival in the W/M group (11.0 weeks) was similar to that in the M/M group (8.0 weeks), and was significantly shorter than in the W/W group (18.0 weeks) (p < 0.002). High-sensitivity KRAS mutation testing is useful for selecting true responders to cetuximab.

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Citations

Mar 27, 2013·Experimental and Molecular Pathology·K PerezP Quesenberry
Sep 12, 2013·Journal of Clinical Pathology·Umberto MalapelleGiancarlo Troncone
Nov 5, 2014·Expert Review of Molecular Diagnostics·Laura Caberlotto, Mario Lauria
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Jan 31, 2013·Clinical Pharmacology and Therapeutics·D Gonzalez de CastroP Workman
Feb 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Munira F Fouz, Daniel H Appella

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