Real-world data of off-label drug use in patients with actionable genomic alterations on next-generation sequencing

Introduction We analyzed the outcomes of patients with advanced cancers in our institution treated with off-label drugs targeting actionable genomic alteration based on next-generation sequencing who did not qualify for clinical trials. Purposes Our study endpoint was objective tumor response or stable disease at 16 weeks or later after treatment initiation. Methods Sixteen patients were included, 8 treated with immune checkpoint inhibitors targeting PD-L1 expression or TP53 mutations and 8 with other drugs. Tumors were analyzed based on PD-L1 expression, TP53 mutation, MSI, TMB, MMR status, and other targetable alterations. Results Of the 16 patients in the intention-to-treat group, no patients had an objective response after 16 weeks. Eleven patients met the primary study endpoint with stable disease, 8 in the immune checkpoint inhibitors group and 3 in the non-immune checkpoint inhibitors group. Using the log-rank test, the p-value for the difference between groups was 0.008. Conclusions In this study with off-label drugs, immune checkpoint inhibitors targeting TP53 mutations or PD-L1 expression were superior to the other drugs. This suggests the possibility of off-label use of anti-cancer drugs based on next-generation sequencing to be beneficial for advanced cancer patients without other therapeutic options.