Cetuximab + First-Line Chemo Benefits Patients with KRAS G13D-Mutant Metastatic Colorectal Cancer
(ChemotherapyAdvisor) – Adding cetuximab to first-line chemotherapy appears to provide a benefit to patients with metastatic colorectal cancer with KRAS G13D–mutant tumors, a study reported in the Journal of Clinical Oncology online June 25 has found.
“This study aimed to validate, in an independent series and in the first-line setting, our previously reported finding of improved clinical outcome for patients with KRAS G13D–mutant tumors receiving cetuximab for chemorefractory metastatic colorectal cancer,” the investigators wrote.
Individual data from 1,378 evaluable patients from the randomized CRYSTAL and OPUS studies were pooled and associations between tumor KRAS mutation status (wild-type, G13D, G12V, or other mutations) and progression-free survival (PFS), survival, and response investigated. A total of 533 patients (39%) had KRAS-mutant tumors; mutations included 83 (16%) with G13D, 125 (23%) with G12V, and 325 (61%) with other mutations.
They found significant variations in treatment effects for tumor response (P=0.005) and PFS (P=0.046) in patients with G13D-mutant tumors vs all other mutations (including G12V). “Within KRAS mutation subgroups, cetuximab plus chemotherapy vs chemotherapy alone significantly improved PFS (median, 7.4 vs 6.0 months; HR, 0.47; P=0.039) and tumor response (40.5% vs 22.0%; OR 3.38; P=0.042) but not survival (median, 15.4 vs 14.7 months; HR, 0.89; P=0.68) in patients with G13D-mutant tumors,” they wrote.
Patients with KRAS G13D–mutated tumors receiving chemotherapy alone experienced worse outcomes (response, 22.0% vs 43.2%; odds ratio, 0.40; P=0.032) than those with other mutations.
“These findings support those previously reported in chemorefractory patients,” the investigators wrote. “Currently, the value of KRAS testing is unprecedented, with tumor KRAS status as the only clinically validated biomarker for the efficacy of treatment with cetuximab.”