Table 2. Treatment of 34 patients (62%) based on molecular profiling with PFS1/PFS0 >1.0°.
Tumor§ | Genetic profile | IHC | Therapy | Evidence supporting treatment decision | |
---|---|---|---|---|---|
CUP | Atypical ALK rearrangement | MET+, PR+ | Crizotinib Tamoxifen | [19, 20] | |
CUP | KITmutation | KIT+ | Imatinib | [21] | |
CUP | mTOR+ | Everolimus | [22, 23] | ||
Thyroid | BRAF mutation (V600E) | Vemurafenib | [24] | ||
Thyroid | mTOR+ EGFR+ |
Temsirolimus Cetuximab | [25, 26] | ||
Thyroid | PDL-1+ | Pembrolizumab | [27, 28] | ||
CCC | EGFR+ (RAS wildtype) | Irinotecan Cetuximab | [29] | ||
CCC | EGFR+ (RAS wildtype) | Irinotecan Cetuximab | [29] | ||
CCC | EGFR+ (RAS wildtype) | Irinotecan Cetuximab | [29] | ||
CCC | FGFR2 mutation | MET+ | Regorafenib | [30, 31] | |
HCC | EGFR+ | Irinotecan Cetuximab | [32, 33] | ||
HCC | EGFR+ | Folfox Cetuximab | [34] | ||
GEC | HER2+ | Trastuzumab Pertuzumab | [35] | ||
GEC | HER2+ | Folfiri Trastuzumab | [35] | ||
CRC | PDL1– MSHI high |
Pembrolizumab* | [36-38] | ||
CRC | MSHI high | Pembrolizumab* | [36-38] | ||
CRC | MET+ mTOR+ | Temsirolimus Bevacizumab beyond progression | [26] | ||
CRC | KIT mutation | MET+ | Sunitinib | [39] | |
RRC | EGFR+ HER2+ HER3+ |
Trastuzumab Lapatinib | [40] | ||
Prostate | mTOR+ | Temsirolimus | [25, 41] | ||
H&N | PDL-1+ | Pembrolizumab* | [42, 43] | ||
H&N | mTOR+ | Carboplatin Everolimus | [44, 45] | ||
H&N | PDGFRa+ | Docetaxel Sunitinib | [46] | ||
NHL | mTOR+ | Everolimus | [22, 23] | ||
NHL | CD30+ | Brentuximab | [47] | ||
Ovarian | ER+ PR+ PDGFa+ mTOR+ |
Letrozol Bevacizumab | [48, 49] | ||
Myeloma | PDL-1+ | Pembrolizumab | [50] | ||
SCLC | EGFR mutation | EGFR + | Afatinib | [51] | |
Pleuramesothelioma | PDL-1 + | Pembrolizumab | [52] | ||
Pleuramesothelioma | PDGFRa+ PDGFRb+ |
Sunitinib | [39, 53] | ||
Pleuramesothelioma | PDGFRb+ | Palbociclib | [54] | ||
PEComa | PDGFRa+ PDGFRb+ EGFR+ |
Sunitinib | [39, 55] | ||
Endometrial | ER+ mTOR+ | Exemestan Everolimus | [56] | ||
Vulva | PDL-1+ | Pembrolizumab | [52] |
§CUP: cancer of unknown primary, CCC: cholangiocarcinoma, HCC: hepatocellular carcinoma, GEC: gastroesophageal cancer, CRC: colorectal cancer, RRC: renal cancer, H&N: head and neck cancer, SCLC: small cell lung cancer, NHL: non Hodgkin lymphoma, PEComa: perivascular epithelioid cell tumor of the kidney.
°The cut-offs values for the selection of putative druggable targets were determined as follows: PDL-1: presence of positive tumor cells, Tumor Proportion Score ≥1, mTOR: IHC score: 200–300, HER2: score ≥2 and confirmed amplification by FISH, KIT: IHC Score 100–300, PR: Allred Score ≥6, EGFR: IHC score 200–300, PDGFRα: IHC score 100–300, PDGFRβ: IHC score 200–300, ER: Allred Score ≥3, CD30: % of positive lymphoma cells, MET: IHC Score ≥2+ and HER3: IHC Score 100–300.
*At the time of treatment decision, pembrolizumab was not approved by neither the (U. S. Food and Drug Administration) FDA nor the European Medicines Agency (EMA).