gms | German Medical Science

Objective: Cancer therapy has dramatically changed over the past decades thanks to the discovery of driver mutations that aid in the development of targeted therapies. KRAS, a proto-oncogene, is involved into the propagation of growth factors and has been associated with lower response of adenocarcinomas to therapies with monoclonal antibodies such as cetuximab and panitumumab, or tyrosine-kinase inhibitors such as erlotinib and gefitinib. Nevertheless, the majority of the studies assessing the role of KRAS mutation in adenocarcinoma have been conducted on primary tumors, excluding brain metastases. In this study, we aimed to elucidate whether KRAS mutation status in brain metastases from adenocarcinomas could predict outcome.

Methods: We analyzed patients enrolled in the prospective Metastasys trial harboring brain metastases from adenocarcinomas of the lung and colon who underwent KRAS mutation analysis in brain specimens. Analysis was performed with real-time PCR assays for KRAS exon 2. Overall survival was calculated, and survival curves of patients harboring mutations were compared to those of patients labeled as KRAS wild type. Statistical analysis was performed with IBM® SPSS® Version 21.

Results: A total of 36 patients harboring adenocarcinoma brain metastases were included. Mean age was 65 years (range: 48-89). Most primaries were adenocarcinomas of the lung (n=24/36, 66.7%). Most patients were males (n=22/36, 61.1%). KRAS mutation was observed in n=19/36, 52.8% of cases. KRAS-mutated and KRAS-wild type groups were matched for histology and adjuvant therapy received postoperatively (one-way ANOVA analysis revealed no statistically significant difference). Median overall survival was 18 months (range: 0.5-143.9 months). KRAS mutated subjects had median overall survival of 11.5 months (range: 0.5-47.2 months). KRAS wild type subjects had median overall survival of 15.0 months (range: 0.5 – 143.9 months). A log rank test did not reveal a statistically significant difference among both groups, χ2(2)=.235, p=.628.

Conclusion: Our results do not support the notion that KRAS mutation has a major impact on survival in patients harboring adenocarcinoma brain metastases undergoing surgical resection. Further prospective trials with a larger cohort are needed to assess the role of KRAS mutation in brain metastases.