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Author(s) -
Michal Navoth,
Adv
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61157
Subject(s) - citation , library science , computer science , information retrieval
Data from four trials of EGFR tyrosine kinase inhibitors (EGFR TKIs) compared with placebo (NCIC CTG BR.21, TOPICAL, NCIC CTG BR.26, and NCIC CTG BR.19) in non– small cell lung cancer (NSCLC) patients were pooled to analyze the prognostic and predictive roles of KRAS mutations (KRAS-MUT) as well as the significance of mutation subtypes. KRAS mutation was found in 20% of the 1362 patients with known KRAS status. No difference in overall survival (OS) was observed in the placebo arms with KRASMUT or wild-type (WT) tumors (hazard ratio, HR 1.04 for univariate, and 1.09 for multivariate analysis). Longer OS was observed in patients with G12C/G12V mutations vs. those with G12D/G12S or G12A/G12R (median OS: 6.3, 1.8, 3.9 months respectively; p 1⁄4 0.01). In the EGFR-TKI arm, no OS benefit was found in patients with KRAS-MUT tumors (OS HR 1.13; PFS HR 1.02). Significant interaction between KRAS status and EGFR-TKI effect was determined for PFS (p 1⁄4 0.04), but not OS (p 1⁄4 0.17). EGFR-TKI therapy was harmful for patients with G12V MUT (OS HR 1.96; p 1⁄4 0.04) but provided OS benefit in those with G12D/G12S (HR 0.49; p 1⁄4 0.05). In summary, the results indicate that KRAS MUT is overall not of prognostic or predictive value for NSCLC patients treated with EGFR-TKIs. The heterogeneity of prognostic and predictive effects of KRAS MUT subtypes in this study warrants further prospective analysis. (p. 312) Number At Risk(G12AR)