Larotrectinib is the first approved selective oral pan-TRK inhibitor with high potency against TRKA, TRKB, and TRKC.229 Entrectinib (RXDX-101/NMS-E628) is a potent multikinase inhibitor targeting TRKA/B/C, ROS1, and ALK.230 Both agents received the FDA breakthrough therapy identification; this breakthrough designation highlights the efficacy of TRK inhibitors in various cancers that have the same mutation, regardless of cancer type and patient age. The gene discussed is ALK; the disease is cancer.