TABLE 3

Clinical characteristics, targeted drugs and efficacy of other actionable oncogenic drivers in nonsmall cell lung cancers

GeneGenomic alterationPrevalence in CaucasiansClinical featuresSelected drugs with clinical data availableRRSelected next-generation drugs overcoming acquired resistanceRR of next-generation drug
ROS1Rearrangements [31]
>9 fusion variants
CD74 (3′)–ROS1 (5′)
  most frequent
1–2% [31]AD (rarely SCC) [31]
Never or light smokers
Younger age
Females>males
Crizotinib72–80% [32, 33]Lorlatinib, cabozantinib, ceritinib, entrectinib, brigatinib, foretinib33%# [29]
BRAFSensitising kinase domain activating mutations [34]
 V600E (50% of all cases)
2–4% [34]Mainly AD [34]
Smokers>nonsmokers
Irrespective of age/sex
Vemurafenib, dabrafenib, trametinib32–63% [35, 36]
METAmplification (ratio ≥5) [37]∼3–4% [37]Mostly AD [37]
Smokers∼nonsmokers
Older age
Females∼males
Crizotinib, cabozantinib, capmatinib67% [38]
Exon 14 mutations [39, 40]2–3% [37, 39, 40]AD∼SCC [41]
Smokers∼nonsmokers
Older age
Females∼males
Crizotinib, cabozantinib, capmatinib44% [42]
RETRearrangements [43, 44]
>4 fusion variants
KIF5B (3′)–RET (5′)
  most frequent
∼1% [44]AD (rarely SCC) [43, 44]
Never or light smokers
Younger age
Females>males
Cabozantinib, vandetanib, lenvatinib, sorafenib, sunitinib, alectinib, ponatinib16–53% [45–48]
NTRKRearrangements [49]
2 fusion variants
MPRIP (3′)–NTRK1 (5′)
CD74 (3′)–NTRK1 (5′)
1% [50, 51]Mainly AD [50, 51]
Smokers>nonsmokers
Irrespective of age/sex
Entrectinib, LOXO-01Strong responses in small cohorts and isolated case reports
HER2Kinase domain activating mutations: [52, 53]
 Exon 20 insertions
1–3% [52, 53]AD [52, 53]
Never or light smokers
Younger age
Females>males
Afatinib, dacomitinib, neratinib, trastuzumab, TDM110–20% [54, 55, 56, 57]

RR: response rate; AD: adenocarcinomal; SCC: squamous cell carcinoma.#: lorlatinib data from a small cohort (n=6) of crizotinib-resistant, ROS1+ lung cancers.