ROS1 | Rearrangements [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 | Crizotinib | 72–80% [32, 33] | Lorlatinib, cabozantinib, ceritinib, entrectinib, brigatinib, foretinib | 33%# [29] |
BRAF | Sensitising kinase domain activating mutations [34] V600E (50% of all cases) | 2–4% [34] | Mainly AD [34] Smokers>nonsmokers Irrespective of age/sex | Vemurafenib, dabrafenib, trametinib | 32–63% [35, 36] | | |
MET | Amplification (ratio ≥5) [37] | ∼3–4% [37] | Mostly AD [37] Smokers∼nonsmokers Older age Females∼males | Crizotinib, cabozantinib, capmatinib | 67% [38] | | |
Exon 14 mutations [39, 40] | 2–3% [37, 39, 40] | AD∼SCC [41] Smokers∼nonsmokers Older age Females∼males | Crizotinib, cabozantinib, capmatinib | 44% [42] | | |
RET | Rearrangements [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, ponatinib | 16–53% [45–48] | | |
NTRK | Rearrangements [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-01 | Strong responses in small cohorts and isolated case reports | | |
HER2 | Kinase 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, TDM1 | 10–20% [54, 55, 56, 57] | | |