Table I.

Currently approved ALK-TKIs.

Drug	FDA approval	EMA approval	Generation	Line of treatment	Targets	Broad indications	Company agreements
Crizotinib	2011	2012	First	First-line	ALK, ROS1, and MET	Metastatic NSCLC	Pfizer
Ceritinib	2014	2015	Second	First-line	ALK, IGF-1R, InsR, and ROS1	Metastatic NSCLC with ALK-positive tumours	Novartis
Brigatinib	2017	2018	Second	First-line	ALK, ROS1, IGF-1R, and FLT-3 as well as EGFR deletion and point mutations.	ALK-positive metastatic NSCLC	Ariad
Alectinib	2015	2016	Second	First-line	ALK and RET with CNS activity.	ALK-positive metastatic NSCLC	Hoffmann-La Roche
Lorlatinib	2018	2019	Third	–	ALK and ROS1 as well as TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK	ALK-positive metastatic NSCLC	Pfizer INC
Entrectinib	2019	2019	Second	First-line	(Trk) A/B/C, ROS1, NTRK, and ALK	Metastatic NSCLC with ROS1-positive tumours	Genentech

ALK-TKIs, anaplastic lymphoma kinase tyrosine kinase inhibitors; NSCLC, non-small-cell lung cancer; EGFR, epidermal growth factor receptor; ROS1, c-ros oncogene 1; MET, mesenchymal-epithelial transition factor; IGF-1R, the insulin-like growth factor-1 receptor; RET, rearranged during transfection; CNS, central nervous system; Trk A/B/C, tropomyosin receptor kinases A/B/C; NTRK, neurotrophic tyrosine receptor kinase.