When is KRAS or TP53 mutation predictive of response to immunotherapy for lung cancer?

Programmed Cell Death Protein-1 (PD-1) checkpoint immunotherapy is a relatively new systemic treatment modality for advanced non-small lung cancer (NSCLC) (1,2). To date, pembrolizumab, nivolumab and atezolizumab have been approved by the United States Food and Drug Administration for this indication either in the front-line or relapsed setting. PD-1 checkpoint, an important immunosuppressive mechanism, is exploited by some tumors to evade immune surveillance. Therefore, by blocking of the PD-1 pathway, an effective immune response against the tumors can be mounted. Nevertheless, PD-1 blockade produces tumor responses in only 20–30% of NSCLC patients. The reason for this is not entirely understood. The presence of PD-L1 protein on tumor cells, while predictive of tumor response, is not a necessary factor. To date, several factors, ranging from clinical characteristics such as smoking status to molecular markers such as tumor mutational burden (TMB) or the presence/absence of some mutations, have been linked to tumor response following PD-1 blockade immunotherapy (3).