This benefit with regards to objective response was observed in advanced NSCLC patients with high TML treated with anlotinib plus immunotherapy (≥10 Muts/Mb 85.7% vs. <10 Muts/Mb 63.6%) in a phase 1 study24 and was also reported in pretreated advanced biliary tract cancer patients.51 However, the mechanism whereby anlotinib favors patients with high genomic instability and the prognostic significance of TML and EGFR gain remain to be investigated. The gene discussed is EGFR; the disease is biliary tract neoplasm.