Table 1.
Systemic, targeted and immunotherapy treatments used to treat patients with breast, melanoma, non-small cell lung, renal cell, prostate, and thyroid cancers
| Histology | Subtype | Incidence of distant metastases at presentation | Early vs. late manifestation | Radiosensitivity | Systemic treatment options | Investigational treatment options |
|---|---|---|---|---|---|---|
| Breast cancer | HR+ HER2+ 10% cases | 37.9% | 3 Months | RS | Endocrine therapy | - |
| ER antagonist tamoxifen | ||||||
| Aromatase inhibitors | ||||||
| LHRH analogs | ||||||
| Estrogen degraders | ||||||
| HR- HER2+ 4% cases | 44.7% | 2 Months | - | Taxanes with | Palbociclib | |
| Humanized MAB: trastuzumab, pertuzumab, lapatinib, tucatinib, neratinib +/- capecitabine | HDACi entinostat, vorinostat | |||||
| PI3Ki buparlisib, pilaralisib | ||||||
| Anti-VEGFR bevacizumab | mTORi everolimus, sirolimus | |||||
| HSP90 inhibitors | Immunotherapy HER2 derived peptide | |||||
| HR+ HER2- 68% cases | 30.6% | 28 Months | - | Endocrine sensitive: | - | |
| Endocrine therapy selective estrogen receptor modulators or downregulators, aromatase inhibitors | ||||||
| CDK4/6 inhibitors: Palbociclib, ribociclib, abemaciclib | ||||||
| PIK3CA mutant: alpelisib + fulvestrant | ||||||
| Endocrine resistant: | ||||||
| Capecitabine | ||||||
| Platinum | ||||||
| Doxorubicin | ||||||
| PARPi talazoparib | ||||||
| HR- HER2- 10% cases | 12.2% | 45.5 Months | - | Capecitabine | PDL1+ pembrolizumab with chemotherapy | |
| Platinum +/- etoposide | PDL1- chemotherapy | |||||
| Doxorubicin | PARPi Olaparib, veliparib, talazoparib | |||||
| Methotrexate, high dose | EGFRi | |||||
| MAB | ||||||
| Sacituzumab govitecan | ||||||
| Melanoma | BRAFV600E | - | - | RR | Dacarbazine | BRAFi dabrafenib, vemurafenib, encorafenib |
| MEKi trametinib, selumetinib, cobimetinib, MEK162 | ||||||
| BRAFi + MEKi | ||||||
| Anti-CTLA4 ipilimumab | ||||||
| PD-1 nivolumab, pembrolizumab | ||||||
| T-VEC + GMCSF | ||||||
| BRAFV600E negative | - | - | - | - | Anti-CTLA4 ipilimumab | |
| PD-1 nivolumab, pembrolizumab | ||||||
| T-VEC + GMCSF | ||||||
| Non-small cell lung cancer | EGFRmut | - | - | RR | Paclitaxel kanglaite | EGFRi afatinib, osimertinib, gefitinib, erlotinib |
| Bevacizumab | ||||||
| EML4-ALK | - | - | - | - | Crizotinib | |
| - | - | - | Fluvastatin | PI3Ki buparlisib | ||
| RANKL MAB denosumab bisphosphonates i.e. | BRAFi dabrafenib for BRAFV600E, MAP2Ki, HER2i | |||||
| MET/VEGFR2i cabozantinib | ||||||
| Zoledronic acid | CTLA4 ipilimumab tremelimumab | |||||
| Platinum based | Anti PD1 nivolumab, pembrolizumab | |||||
| Renal cell | Clear cell VHL/VEGFR, PBRM1, SETD2, BAP1, mTOR | - | - | RR | Bevacizumab/IFN alpha | VEGFR/PDGFRi Axitinib, pazopanib, sorafenib, sunitinib |
| IL2 | Cabozantinib VEGFR/AXL/cMeti | |||||
| Pazopanib, sunitinib or temsirolimus | Lenvatinib FGFR/VEGFRi/everolimus | |||||
| PD-1/PD-L1 Nivolumab, ipilimumab | ||||||
| Everolimus/sorafenib | ||||||
| mTORi everolimus, temsirolimus | ||||||
| Papillary MET NRF2 | - | - | - | - | - | |
| TP53, PTEN, CDKN2A loss, SMARKB1 loss, TFE3-TFEB fusion | - | - | - | - | - | |
| Prostate cancer | - | - | - | RS | Androgen receptor antagonist flutamide, bicalutamide, abiraterone, ketoconazole | |
| LHRH agonist/antagonist leuproline, goserelin, degarelix | ||||||
| Androgen resistant | - | - | - | Doxorubicin | EGFRi gefitinib, erlotinib | |
| Docetaxel | EGFR/HER2i lapatinib | |||||
| Cabazitaxel mitoxantrone | EGFR MAB cetuximab | |||||
| MET/VEGFR2 cabozantinib | ||||||
| PARPi Olaparib | ||||||
| RANKL denosumab | ||||||
| antiCTLA4 ipilimumab | ||||||
| antiPD1/PD-L1 nivolumab, pembrolizumab, atezolizumab | ||||||
| Sipuleucel-T vaccine | ||||||
| Thyroid cancer | Differentiated thyroid carcinoma | - | - | RR | - | VEGFR/Flt3/RET/cKIT/BRAFi Sorafenib |
| VEGFR/FGFR/PDGFR/KIT/RETi Lenvantinib | ||||||
| Anaplastic carcinoma | - | - | - | - | - | |
| Medullary thyroid carcinoma | - | - | - | - | VEGFR/EGFR/RETi Vandetanib | |
| VEGFR2/cMet/AXL/RETi Cabozantinib | ||||||
| - | - | - | - | PI3Ki | ||
| HER2/3-ALK translocations | ||||||
| antiCTLA4 | ||||||
| anti-PD1 |
HR, hormone receptor; HER2, human epidermal growth factor receptor 2; RR, radiation resistant; RS, radiation sensitive; ER, estrogen receptor; LHRH, luteinizing hormone releasing hormone; MAB, monoclonal antibody; HDACi, histone deacetylase inhibitor; PI3Ki, phosphatidylinositol-3-kinase inhibitor; mTORi, mammalian target of rapamycin inhibitor; CDK4/6, cyclin dependent kinases 4/6; PARPi, poly-ADP-ribose polymerase inhibitor; PDL1, programmed death ligand 1; EGFRi, epidermal growth factor receptor inhibitor; BRAFi, v-Raf murine sarcoma viral oncogene homolog B1 inhibitor; MEKi, mitogen activated protein kinase kinase inhibitor; MEK162, mitogen activated protein kinase kinase 162; CTLA4i, cytotoxic T lymphocyte associated protein 4 inhibitor; PD-1, programmed cell death protein 1; T-VEC, talimogene; GMCSF, granulocyte macrophage colony stimulating factor; RANKL, receptor activator of nuclear factor kapppa-B ligand; VHL, von Hippel Lindau; VEGFR, vascular endothelial growth factor receptor; PBRM1, polybromo 1; SETD2, su(var), enhancer of zeste, trithorax - domain containing 2; BAP1, ubiquitin carboxyl-terminal hydrolase 1; FGFR, fibroblast growth factor receptor; VEGFRi, vascular endothelial growth factor inhibitor; TP53, tumor protein p53; PTEN, phosphatase and TENsin homolog deleted on chromosome 10; CDKN2A, cyclin dependent kinase inhibitor 2A; SMARCB1, SWI/SNF related, matrix associated, actin dependent regulator of chromatin; TFE3, transcription factor enhancer 3; TFEB, transcription factor EB; RET, rearranged during transfection; PDGFR, platelet derived growth factor receptor; RETi, rearranged during transfection inhibitor; ALK, anaplastic lymphoma kinase.