Table 3 Actionability provided by germline and somatic tissue and liquid biopsy-based.
Patient # | Diagnosis | Treatment | Follow-up | Other types of actionability | |||||
|---|---|---|---|---|---|---|---|---|---|
ESCAT tier | Tissue biopsy | Liquid biopsy | Clinical trials | Tissue biopsy | Liquid biopsy | Tissue biopsy | Liquid biopsy | ||
1 | NSCLC (adenocarcinoma) | IV-A | KRAS p.Gly12Val cobimetinib, binimetinib, trametinib | — | NCT03170206, NCT04735068, NCT03948763 | ATR p.Leu341Phe / EGFR p.Gly517Cys / GNA11 p.Glu245Lys / IGF1R p.Glu979* / KRAS p.Gly12Val / MET p.Asp1222Asn / ROS1 p.Met1118Ile / TP53 p.Phe341_Arg342delinsLeu | FGFR2 p.Glu777Lys | KRAS p.Gly12Val PROGNOSIS | — |
2 | NSCLC (adenocarcinoma) | I-A | EGFR p.Glu746_Ala750del afatinib, dacomitinib, erlotinib, erlotinib + ramucirumab, gefitinib, osimertinib | — | NA | EGFR p.Glu746_Ala750del | BRAF N486_T491>K | — | — |
III-B | — | BRAF N486_T491>K dabrafenib + trametinib | NCT04620330 | ||||||
3 | NSCLC (poorly differentiated carcinoma) | — | — | — | — | BAP1 p.Ala134Thr / JAK1 p.Ser1137Pro / TP53 p.Tyr220Cys | — | — | — |
4 | NSCLC (squamous cell carcinoma) | III-A | PIK3CA p.Glu542Lys alpelisib + fulvestrant (other tumour) | NCT04073680, NCT04774952 | IL7R p.Lys395Arg / PIK3CA p.Glu110Lys / PIK3CA p.Glu542Lys / RET p.Pro1053Ser / TP53 p.Gln331* | PIK3CA p.Glu542Lys | EXT1 p.Tyr119* GENETIC COUNSELLING | — | |
III-A | PIK3CA p.Glu110Lys alpelisib + fulvestrant (other tumour) | — | NCT04073680, NCT04774952 | ||||||
5 | Pilomatrix carcinoma | III-A | CTNNB1 p.Asp32Tyr everolimus + letrozole, imatinib, vinorelbina (other tumour) | — | — | CSF1R p.Arg579Trp / CTNNB1 p.Asp32Tyr / FGFR4 p.Arg606Gln / TP53 p.Arg248Trp | — | BRIP1 p.Phe176Serfs*9 GENETIC COUNSELLING | — |
III-A | BRIP1 p.Phe176Serfs*9 olaparib (other tumour) | — | NCT04171700 | ||||||
6 | Colon adenocarcinoma | III-A | FBXW7 p.Arg465Cys temsirolimus, veliparib, sirolimus, everolimus, (other tumour) | — | — | FBXW7 p.Arg465Cys / KDR p.Gln268Lys / TP53 p.Arg273Cys | TP53 p.Arg273Cys | — | — |
7 | Uterine leiomyosarcoma | — | — | — | — | TP53 p.Pro27Leufs*17 | TP53 p.Pro27Leufs*17 | — | — |
8 | Squamous cell carcinoma of the cervix | III-A | PIK3CA amplification N=6, PIK3CA p.Glu542Lys alpelisib + fulvestrant (other tumour) | - | NCT04073680, NCT04774952, NCT04836663 | PIK3CA p.Glu542Lys | — | — | — |
9 | Clear cell renal cell carcinoma | — | — | — | — | CSF3R p.Asp172Asn | — | — | — |
10 | Uterine carcinosarcoma | III-A | BRCA1 p.Gln1111Asnfs*5 niraparib, olaparib, rucaparib, talazoparib (other tumour) | — | NCT04171700, NCT03552471 | PIK3R1 p.Arg358Pro / PIK3R1 p.Gln579* / TP53 c.993+1G>A | — | BRCA1 p.Gln1111Asnfs*5 GENETIC COUNSELLING | — |
IV-A | PIK3R1 p.Gln579* PI3K inhibitors, mTOR inhibitors, AKT inhibitors | — | NCT04836663 | ||||||
12 | Adenocarcinoma of the bladder | IV-A | KRAS amplification N=9 cobimetinib, binimetinib, trametinib | — | NCT03634982 | TP53 p.Cys275Arg | — | CCND1 amplification N = 7PROGNOSIS | — |
13 | NSCLC (squamous cell carcinoma) | III-A | PTEN p.Gly165Glu everolimus, tensirolimus (other tumours) | — | NCT04591431, NCT02465060 | IGF2 p.Thr40Asn / JAK3 c.566+1G>T / MTOR p.Ala1971Val / PTEN p.Gly165Glu / TP53 p.Pro250Leu / TSC2 p.Arg344Met | — | — | — |
14 | NSCLC (squamous cell carcinoma) | III-A | MAP2K1 p.Lys57Asn trametinib (other tumour) | — | NCT04488003 | MAP2K1 p.Lys57Asn / TP53 p.Arg156Pro | TP53 p.Arg156Pro | — | — |
15 | NSCLC (adenocarcinoma) | I-A | KRAS p.Gly12Cys sotorasib | — | NA | CCND3 p.Arg33Cys / KRAS p.Gly12Cys | — | KRAS p.Gly12Cys PROGNOSIS | — |
16 | SCLC | III-A | — | PTEN p.His61Arg, PTEN c.635-1G>C everolimus, tensirolimus (other tumours) | NCT04774952, NCT04591431 | MTOR p.Gly1064Glu / IL7R p.Gly215Phe / ROS1 p.Ser1279Cysfs*51 / TP53 c.560-2A>G | PTEN p.His61Arg / PTEN c.635-1G>C / TP53 c.560-2A>G | — | — |
17 | Colon adenocarcinoma | III-A | NF1 p.Gln786* selumetinib, trametinib (other tumour) | — | NCT02465060 | KRAS p.Gly13Asp / MITF p.Arg406Gln / NF1 p.Gln786* / NF1 p.Ala1429Thr / PIK3CA p.Glu545Lys / TP53 p.Cys229Tyrfs*10 | — | — | — |
III-A | PIK3CA p.Glu545Lys alpelisib + fulvestrant (other tumour) | — | NCT04073680, NCT04774952 | ||||||
IV-A / NA (resistance) | KRAS p.Gly13Asp cobimetinib, binimetinib, trametinib / anti-EGFR antibody (resistance) | — | NCT04117087, NCT03948763 | ||||||
18 | NSCLC (adenocarcinoma) | -— | — | — | — | FRS2 p.Asp505Valfs*? / GATA3 p.Ile351Ser / GATA3 p.Gly361Asp / MET p.Asn879Lysfs*23 / PIK3CA p.Asp258Tyr | NF1 p.Ala1716Gly | — | — |
19 | NSCLC (poorly differentiated carcinoma) | — | — | — | — | FBXW7 p.Asp119Tyr / TP53 p.Val157Phe | — | — | — |
20 | NSCLC (adenocarcinoma) | — | — | — | — | STK11 p.Cys132Arg | — | — | — |
21 | Pancreatic ductal adenocarcinoma | III-A | ATM p.Arg2993* olaparib (other tumour) | — | NCT03611868, NCT03742895 | ATM p.Arg2993* / KRAS p.Gly12Arg | — | — | — |
IV-A | KRAS p.Gly12Arg cobimetinib, binimetinib, trametinib | — | NCT04348045, NCT04117087, NCT03948763 | — | — | — | |||
23 | SCLC | — | — | — | — | POLE p.Gln508Ala509delinsHisSer / RET p.Val53Leu / RET p.Gln70Leu / RET p.Arg417Leu / SMO p.Gly65Cys / TP53 p.Arg158Leu | — | — | — |
24 | NSCLC (adenocarcinoma) | I-A | EGFR p.Glu746_Ser752delinsVal afatinib, dacomitinib, erlotinib, erlotinib + ramucirumab, gefitinib, osimertinib | — | NA | EGFR p.Glu746_Ser752delinsVal | — | — | — |
26 | NSCLC (squamous cell carcinoma) | III-A | PTEN p.Glu352* everolimus, tensirolimus (other tumours) | — | NCT04774952 | ERBB4 p.Thr371Asn / FGFR2 c.377-1G>A / GNAS p.Pro22Thr / PTEN p.Glu352* / ROS1 p.His1210Leu / TP53 p.Asp184Glufs*63 | — | — | — |
27 | High-grade transitional cell carcinoma of the bladder | III-A | ARID1A p.Gln2100* berzosertib (other tumour) | — | NCT04953104 | ARID1A p.Gln2100* / CDKN1A p.Pro12Hisfs*19 / CDKN2B p.Asp110Asn / JAK3 p.Asp671Asn / PALB2 p.Glu3* / TP53 p.His179Arg | — | — | — |
III-A | PALB2 p.Glu3* olaparib (other tumour) | — | NCT04171700 | ||||||
28 | Colon adenocarcinoma | IV-A / NA (resistance) | KRAS p.Gly12Val cobimetinib, binimetinib, trametinib / anti-EGFR antibody (resistance) | — | NCT04117087, NCT03948763 | KRAS p.Gly12Val / TP53 p.Lys292Glyfs*52 | PTPN11 p.Val428Met | KRAS p.Gly12Val PROGNOSIS | — |
29 | NSCLC (adenocarcinoma) | III-A | NF1 c.6641+1G>C selumetinib, trametinib (other tumour) | — | NCT02465060 | BRAF p.Asn581Ile / BRCA2 p.His2537Leu / ERBB4 p.Gly727Ala / FGFR4 p.His727Gln / NF1 c.6641+1G>C / NF1 p.Leu1095Phe / POLE c.3583-2A>T / TP53 c.375+1G>T | EGFR p.Gln276His | — | — |
III-A | POLE c.3583-2A>T pembrolizumab, nivolumab (other tumours) | — | NCT02715284 | ||||||
30 | NSCLC (poorly differentiated carcinoma) | IV-A | KRAS p.Gly12Asp cobimetinib, binimetinib, trametinib | — | NCT03170206, NCT04735068, NCT03948763 | GNAS p.Asp466Glu / KRAS p.Gly12Asp / MPL p.Leu234Val / PRKCH p.Asp232Gly / PTEN p.Asp107Val / TP53 p.Arg249Ser / TSC2 p.Val586Leu | — | KRAS p.Gly12Asp PROGNOSIS | — |
31 | NSCLC (squamous cell carcinoma) | IV-A | KRAS p.Gly12Asp cobimetinib, binimetinib, trametinib | — | NCT03170206, NCT04735068, NCT03948763 | ERBB4 p.Gly1272Leu / FANCA p.Arg751Trp / GATA3 p.Arg312Glyfs*44 / KDR p.Ile724Met / KRAS p.Gly12Asp / MAP2K2 p.Val283Glu / MET p.Leu920Pro / PDGFRA p.Val1084Met / PIK3CB p.Ile428Phe / TP53 p.Arg249Trp | — | KRAS p.Gly12Asp PROGNOSIS | — |
32 | NSCLC (adenocarcinoma) | IV-A | KRAS p.Gly12Val cobimetinib, binimetinib, trametinib | NCT03170206, NCT04735068, NCT03948763 | ATR p.Asn973Ser / KRAS p.Gly12Val / MTOR p.Asp2102Val / PTCH1 p.Arg606Met / RAD51C p.Leu61Val / RICTOR p.Arg1670Trp / RICTOR p.Pro1397Ser / TP53 p.Gln317* | KRAS p.Gly12Val | KRAS p.Gly12Val PROGNOSIS | ||
33 | NSCLC (adenocarcinoma) | III-A | PIK3CA p.Glu545Lys alpelisib + fulvestrant (other tumour) | — | NCT04073680, NCT0477495 | ERBB4 p.Arg103His / KDR p.Gly95Arg / MITF (NM_000248) p.Arg197_Ala198del / PIK3CA p.Glu545Lys / PTCH1 p.Val1137Leu / TP53 p.Leu32Valfs*10 | MET 1392+1G>A | — | — |
34 | Pharyngeal squamous cell carcinoma | — | — | — | — | ATR p.Ser1843Phe / TP53 p.Pro190Leu / TP53 p.Glu294* | — | — | — |
35 | Colon adenocarcinoma | III-A | NF1 p.Leu1246Cysfs*20 selumetinib, trametinib (other tumour) | — | NCT02465060 | FLT3 p.Gln338* / KRAS p.Ala146Val / NF1 p.Leu1246Cysfs*20 / TP53 p.Arg175His | — | — | — |
IV-A / NA (resistance) | KRAS p.Gly12Val cobimetinib, binimetinib, trametinib / anti-EGFR antibody (resistance) | — | NCT04117087, NCT03948763) | ||||||
36 | NSCLC (adenocarcinoma) | — | — | — | — | ALK p.Glu657Gln / ARID1A p.Pro526Ser / FLT3 p.Val106Phe / IDH1 p.Gly310Val / IDH2 p.Met293Ile / INPP4B p.Gly146Arg / JAK1 p.Ile928Met / JAK3 p.Asp1025His / MTOR p.Pro574Ser / NF2 p.Glu442Gln / POLE p.Phe695Ile / TP53 p.Arg273Leu | TP53 p.Arg273Leu | — | — |
37 | NSCLC (squamous cell carcinoma) | III-A | PALB2 p.Gly881Valfs*8 olaparib (other tumour) | — | NCT04171700 | KIT p.Arg161Met / PALB2 p.Gly881Valfs*8 / PIK3CA p.Glu542Lys / TP53 p.Arg156Profs*15 | — | — | — |
III-A | PIK3CA p.Glu542Lys alpelisib + fulvestrant (other tumour) | — | NCT04073680, NCT04774952 | ||||||
38 | NSCLC (adenocarcinoma) | — | — | — | — | MET p.Gly872Valfs*4 | — | — | — |
39 | Colon adenocarcinoma | — | — | — | — | IGF1R p.Asp654Val / TP53 p.Asn131Lysfs*42 | TP53 p.Arg249Lys | — | — |
40 | NSCLC (adenocarcinoma) | III-A | ATM p.Tyr2019Cys olaparib (other tumour) | — | NCT03742895 | ATM p.Tyr2019Cys / KDR p.Ser971Arg / KRAS p.Gly12Val / PIK3R1 p.Arg574Ile / SMO p.Leu426Pro / TP53 p.Gly154Val | — | KRAS p.Gly12Val PROGNOSIS | — |
IV-A | KRAS p.Gly12Val cobimetinib, binimetinib, trametinib | — | NCT03170206, NCT04735068, NCT03948763 | ||||||
41 | Colon adenocarcinoma | IV-A / NA (resistance) | KRAS p.Gly12Asp cobimetinib, binimetinib, trametinib / anti-EGFR antibody (resistance) | — | NCT04117087, NCT03948763) | AR p.Met788Leu / ATM p.Leu546Val / CCND3 p.Glu253Asp / ERBB2 p.Ala1216Asp / ERBB3 p.Arg488Gln / IGF1R p.Gly1330Ser / IGF2 p.Arg128Lys / KDR p.Cys482Arg / KRAS p.Gly12Asp / MAP2K1 p.Gly301Arg / TP53 p.Arg267Trp / TP53 p.Arg248Gln | — | KRAS p.Gly12Asp PROGNOSIS | — |
42 | Colon adenocarcinoma | I-A | BRAF p.Val600Glu encorafenib + cetuximab | — | NA | BRAF p.Val600Glu / BRCA2 p.Ala2951Thr / MPL p.Arg592Gln / TP53 p.Ile232del | — | BRAF p.Val600Glu PROGNOSIS | — |
43 | NSCLC (squamous cell carcinoma) | III-A | NF1 p.Arg262Valfs*19 selumetinib, trametinib (other tumour) | — | NCT02465060 | ALK p.Gly939Ser / ARID1A p.Ala1136Ser / ERBB2 p.Ala21Gly / ERBB4 p.Glu547Asp / GNAS p.Arg201Cys / NF1 p.Arg262Valfs*19 / TP53 p.Ser315Leufs*30 | ERBB2 p.Ala21Gly / TP53 p.Ser315Leufs*30 | — | — |
44 | Melanoma | I-A | BRAF p.Val600Glu vemurafenib, dabrafenib, trametinib, dabrafenib + trametinib, vemurafenib + cobimetinib, encorafenib + binimetinib | — | NA | BRAF p.Val600Glu / BRCA2 p.Arg2861Lys | — | BRAF p.Val600Glu PROGNOSIS | — |
45 | NSCLC (squamous cell carcinoma) | IV-A | KRAS p.Gln61Leu cobimetinib, binimetinib, trametinib | — | NCT03170206, NCT04735068 | ALK p.Tyr1092* / ERBB4 p.His470Asp / GNAS p.Ser532Alafs*158 / GNAS p.Ala548Pro / KDR p.Tyr418His / KRAS p.Gln61Leu / TP53 p.Gln192* | — | — | — |
46 | High-grade glioblastoma | III-A | EGFR p.Pro596Leu, EGFR amplification N>25 afatinib, dacomitinib, erlotinib, erlotinib + ramucirumab, gefitinib, osimertinib (other tumour) | — | NCT04933422, NCT03618667 | EGFR p.Pro596Leu / EGFR amplification N>25 / INPP4B p.Ile83Met / MITF p.Arg13* / PTCH1 p.Tyr373* / STAG2 p.Arg604* / TSC1 p.Pro196Arg | — | — | — |
IV-A | PTCH1 p.Tyr373* vismodegib, sonidegib | — | — | ||||||
IV-A | STAG2 p.Arg604* olaparib, veliparib, rucaparib | — | — | ||||||
48 | SCLC | — | — | — | — | TP53 p.Leu145Gln / TSC2 p.Asp1403Glu | TP53 p.Leu145Gln | — | — |
49 | NSCLC (adenocarcinoma) | III-A | POLE c.1686+1G>A pembrolizumab, nivolumab (other tumours) | — | NCT02715284 | KRAS p.Gly12Val / POLE c.1686+1G>A / SH2B3 p.Asp241Asn / STK11 c.374+1A>G / TP53 c.375+1G>A | KRAS p.Gly12Val / TP53 c.375+1G>A | — | — |
III-A | STK11 c.374+1A>G everolimus (other tumour) | — | NCT04173507 | ||||||
IV-A | KRAS p.Gly12Val cobimetinib, binimetinib, trametinib | NCT03170206 | |||||||
50 | SCLC | III-A | KIT p.Asp816Val, KIT p.Asp820Val sorafenib, ponatinib, nilotinib, dasatinib, regorafenib ripretinib, avapritinib | NCT04771520 | KIT p.Asp816Val / KIT p.Asp820Val / TP53 p.Cys135Arg / MTOR p.His1819Asn | KIT p.Asp816Val / KIT p.Asp820Val / TP53 p.Cys135Arg / MTOR p.His1819Asn / GNAS p.Arg547His | — | — | |
