Key Points
• Conclusion/Relevance: “This study reports a significant survival benefit of ICIs over chemotherapy or local control alone in patients with NSCLCBM [NSCLC brain metastases]. This retrospective analysis of patients treated for NSCLCBM has also emphasized the shift away from surgery for management of BM in the age of ICIs. Finally, our data suggests the greatest benefit of ICIs are seen in patients with KRAS mutations in their tumors, which should be considered in future trials.”
• The investigators reviewed data from 800 patients from a major tertiary-care center, with 97% administered stereotactic radiosurgery (SRS) for local treatment of BM. They noted an improvement in OS when patients received ICIs within 90 days of the diagnosis of brain metastases, which indicates that ICIs offer an OS benefit compared with traditional chemotherapy or local therapy alone.
• “In order to identify patient populations who respond best to ICIs, we investigated the impact of KRAS mutation status. We found an improved OS in patients with a KRAS mutation who were treated with ICI within 90 days over no-ICI. This difference was not observed in the patients with wild-type KRAS. A similar result was seen in a meta-analysis of three clinical trials that compared the difference in response to ICIs based on KRAS status,” wrote the authors.
• The retrospective nature of the study was a major limitation. The electronic medical records mined was not designed for research. Mutation and PD-L1 status were based on the primary tumor, and KRAS mutational subtypes were not obtained. The researchers could not determine whether KRAS mutation status was an independent predictor of survival or if the increased PD-L1 expression in these patients yielded survival differences. Furthermore, the non-ICI group was not always treated with any systemic chemotherapy, with almost all patients receiving intracranial SRS. Lastly, the researchers did not specifically investigate intracranial or extracranial response, thus any difference in OS could be secondary to control or non-control of the extracranial disease.

Discussion questions: Based on your experiences, what is the clinical importance of these findings? How do you think the study results would be changed if KRAS mutational subtypes were included by the researchers?