Difference in Outcome between Types of KRAS Mutation May Point toward Difference in Tumor Biology

Abstract

To the Editor: With interest we read the article by Nadal et al. entitled “KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma”. The authors retrospectively studied a group of 179 patients with surgically resected adenocarcinoma of the lung with known KRAS mutational status. The aim of this study was to investigate the effects, if any, of KRAS mutant subtypes on survival probabilities. Here, patients with any KRAS mutation had significant poorer survival compared with patients with KRAS wild type. In particular, patients with a G12C mutation had worse outcome compared with other types of mutation. We would like to comment on this article. First, the authors report that patients with a G12C KRAS mutation have a poorer prognosis compared with other types of KRAS mutations, which is illustrated in Figure 1. The authors also refer to a univariate analysis presented in Table 3 (p.1518). However, the univariate analysis provides a comparison between G12C KRAS mutation and wild type, but not G12C and non-G12C KRAS mutations. A difference in prognosis between types of KRAS mutation could possibly point toward differences in tumor biology. This is relevant data and we would like to invite the author to present the data of a multivariate analysis comparing G12C and other types of KRAS mutations. Furthermore, it is interesting to know how many patients had an EGFR mutation among the patients with KRAS wild type. This group of patient is known to a have favorable prognosis and can provide a relevant bias. We agree that the prognostic value of KRAS mutation is a controversial topic. As discussed in the article, two large studies on KRAS mutational status in resected non–small-cell lung carcinoma did not found a prognostic value for KRAS mutation or types of mutation. Over the past decade, almost a dozen studies investigated the same question in non–smallcell lung carcinoma with conflicting results. The study by Nadal et al. should therefore be interpreted carefully, despite methodological differences. Nonetheless, the data on KRAS addiction is interesting and we hope that future studies will point out the clinical relevance.