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

Genomic featuresFirst-generation ALK TKIRRmPFS monthsSelected next-generation ALK TKIs overcoming crizotinib resistanceClinical trial phase (study acronym)SubjectsContextTrial RRTrial mPFS months
>27 fusion variants [15]
EML4 (3′)–ALK (5′) most frequent
Crizotinib60–74% [16–18]7.7–10.9 [16–18]CeritinibI (ASCEND-1) [19]163TKI resistant56%6.9
II (ASCEND-2) [20]140TKI resistant39%5.7
I (ASCEND-1) [17]83TKI naïve72%18.4
II (ASCEND-3) [21]124TKI naïve63.7%18.4
III (ASCEND-5) [22]231TKI resistant39.1%5.4
AlectinibII (NP28673) [23]138TKI resistant50.8%8.9
II (NP28761) [24]87TKI resistant52.2%8.1
I (AF-001JP)# [25]46TKI naive93.5%27.7
III (J-ALEX)# [26]104TKI naive92%
BrigatinibI/II [27]71TKI resistant72%12.9
II (ALTA) [28]110TKI resistant54%12.9
I/II [27]8TKI naive100%
LorlatinibI/II [29]41+TKI resistant+46%+
EnsartinibI/II [30]25TKI resistant64%
I/II [30]14TKI naive71%

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.