TABLE 2

Clinical characteristics, targeted drugs and efficacy of anaplastic lymphoma kinase (ALK) rearranged nonsmall cell lung cancers

Genomic features	First-generation ALK TKI	RR	mPFS months	Selected next-generation ALK TKIs overcoming crizotinib resistance	Clinical trial phase (study acronym)	Subjects	Context	Trial RR	Trial mPFS months
>27 fusion variants [15] EML4 (3′)–ALK (5′) most frequent	Crizotinib	60–74% [16–18]	7.7–10.9 [16–18]	Ceritinib	I (ASCEND-1) [19]	163	TKI resistant	56%	6.9
					II (ASCEND-2) [20]	140	TKI resistant	39%	5.7
					I (ASCEND-1) [17]	83	TKI naïve	72%	18.4
					II (ASCEND-3) [21]	124	TKI naïve	63.7%	18.4
					III (ASCEND-5) [22]	231	TKI resistant	39.1%	5.4
				Alectinib	II (NP28673) [23]	138	TKI resistant	50.8%	8.9
					II (NP28761) [24]	87	TKI resistant	52.2%	8.1
					I (AF-001JP)^# [25]	46	TKI naive	93.5%	27.7
					III (J-ALEX)^# [26]	104	TKI naive	92%
				Brigatinib	I/II [27]	71	TKI resistant	72%	12.9
					II (ALTA) [28]	110^¶	TKI resistant	54%^¶	12.9^¶
					I/II [27]	8	TKI naive	100%
				Lorlatinib	I/II [29]	41⁺	TKI resistant⁺	46%⁺
				Ensartinib	I/II [30]	25	TKI resistant	64%
				Ensartinib	I/II [30]	14	TKI naive	71%

TKI: tyrosine kinase inhibitor; RR: response rate; mPFS: median progression-free survival. ^#: Japanese study; ^¶: data correspond to brigatinib at 180 mg daily dose; ⁺: including patients resistant to more than one ALK TKI.