The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in non–small cell lung cancer

Pooled Analysis of the Prognostic and Predictive Value of KRAS Mutation Status and Mutation Subtype in Patients with Non–Small Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

“…Both are G / T transversion MUTs that are associated with tobacco exposure. 13,14,25 Our observation regarding a favorable prognosis for patients with G12C/G12V MUTs compared with other codon 12 subtypes is the first to be described in lung cancer. Such an association was not found in the LACE-Bio analyses, nor was it observed in the biomarker analysis of the RADIANT study.…”

“…10,11 Furthermore, KRAS MUTs are not homogeneous, and small retrospective studies suggest that specific KRAS MUTs may be associated with different sensitivity to EGFR TKIs. 9,[12][13][14] We performed this pooled analysis of four academic, cooperative group randomized placebo-controlled trials of EGFR TKI therapy in NSCLC in an attempt to clarify the prognostic and predictive effect of KRAS MUT and MUT subtype on benefit from EGFR TKI therapy. These trials were selected because we had full access to the clinical databases and to all molecular results.…”

KRAS-G12C Mutation Is Associated with Poor Outcome in Surgically Resected Lung Adenocarcinoma

“…15 In advanced lung cancer, KRAS mutations were associated with poor response to EGFR tyrosine kinase inhibitors, 35 and in a small study, KRAS-G12C patients had worse PFS when treated with EGFR tyrosine kinase inhibitors. 36 In addition, advanced NSCLC patients with KRAS mutations did not benefit from maintenance with erlotinib after receiving four cycles of cisplatin-based chemotherapy. 37 Similarly, advanced NSCLC patients with KRAS-G12C and G12V had shorter PFS when treated with targeted therapies in the BATTLE trial.…”

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

“…95 Five studies attempted to identify associations between patient or tumor characteristics and KRAS mutational status. 49,52,92,93,95 Two MAs 93,94 reported on overall survival and EGFR-TKI response rates when KRAS mutationepositive patients were treated with standard care. All included studies were assessed for quality and none were found to have methodologic flaws that would raise concerns about the studies' findings (SDC Table 16).…”