Table I.
Current clinical trials regarding potential targets in triple-negative breast cancer.
| Target pathway/molecules | Chemical agent | Drug class | Combinatorial agents | Clinical trials | Phase | Side effect | (Refs.) |
|---|---|---|---|---|---|---|---|
| EGFR | Afatinib | EGFR-TKI | Paclitaxel | NCT02511847 | II | Gastrointestinal and skin-related side effects | (45) |
| Gefitinib | EGFR-TKI | NCT01732276 | II | Hematological toxicity | (46) | ||
| Lapatinib | EGFR-TKI | Veliparib (PARPi) | NCT02158507 | – | |||
| Panitumumab | EGFR mA | Gemcitabine, carboplatin | NCT00894504 | II | – | ||
| VEGFR | Bevacizumab | VEGFR mA | Carboplatin/cyclophosphamide or paclitaxel | NCT01898117 | II | Hypertension, proteinuria, mild to moderate bleeding, delayed wound healing, thromboembolic events, nasal septum perforation | (47) |
| Apatinib | VEGFR2 | NCT01176669 | II | A favourable side effect profile | (48) | ||
| Cediranib maleate | pan-VEGFR | Olaparib (PARPi) | NCT01116648 | I/II | Chest pain, fatigue, thrombocytopenia, hypertension, hemoptysis | (49) | |
| HGFR/c-MET | Tivantinib | c-MET-TKI | NCT01575522 | II | Toxicity was minimal with anemia, fatigue and grade 3/4 neutropenia | (50) | |
| RTKs | Cabozantinib | VEGFR-MET | NCT01738438 | II | Fatigue, diarrhea, mucositis, and palmar-plantar erythrodysesthesia | (51) | |
| Lucitanib | VEGFR-FGFR-PDGFR | NCT02202746 | II | Hypertension, asthenia, proteinuria and thrombotic microangiopathy | (52) | ||
| PI3K/AKT/mTOR pathway | BKM120 | pan-PI3K | Capecitabine | NCT02000882 | II | Hyperglycemia, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase increase | (53) |
| BKM120 | pan-PI3K | NCT01629615 | II | Hyperglycemia, alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase increase | (53) | ||
| BKM120/BYL719 | PI3K | Olaparib (PARPi) | NCT01623349 | I | Hyperglycemia, alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase increase | (53) | |
| Taselisib | PIK3CA | Enzalutamide (ARi) | NCT02457910 | I/II | Diarrhea, hyperglycemia, decreased appetite, nausea, rash, stomatitis and vomiting | (54) | |
| AZD8186 | PI3K | AZD2014 (EGFR-TKI), abiraterone acetate | NCT01884285 | I | – | ||
| ARQ 092 | pan-AKT | Carboplatin, paclitaxel | NCT02476955 | I | – | ||
| AZD5363 | AKT | Paclitaxel | NCT02423603 | II | Diarrhea, hyperglycemia, nausea and maculopapular rash | (55) | |
| MK2206 | AKT | NCT01319539 | II | Dose-limiting toxicities: Mucosal inflammation, hyponatremia, face edema, erythema multiforme and hyperglycemia. Common adverse events: Rash, an elevated insulin c-peptide level, stomatitis, pyrexia, eosinophilia, leukopenia and hyperglycemia | (56) | ||
| Ipatasertib | pan-AKT | Paclitaxel | NCT02162719 | II | Gastrointestinal adverse events | (57) | |
| Everolimus | mTOR | Eribulin | NCT02616848 | I | Mucositis, hyperglycemia, non-infectious pneumonitis and hematological toxicity | (58) | |
| Temsirolimus | mTOR | Neratinib (EGFRi) | NCT01111825 | I/II | Fatigue, edema, anorexia, nausea, rash, mucositis and lymphopenia | (59) | |
| AR | GTx-024 | AR | NCT02368691 | II | – | ||
| Bicalutamide | AR | NCT02348281/NCT02353988 | II | Well tolerated | |||
| Enzalutamide | AR | Paclitaxel | NCT02689427 | II | Well tolerated | (60) | |
| BRCA | Rucaparib | PARP | Cisplatin | NCT01074970 | II | Well tolerated | (61) |
| mutation | E7449 | PARP | Temozolomide/carboplatin, paclitaxel | NCT01618136 | I/II | – | |
| Iniparib | PARP | Gemcitabine, carboplatin | NCT01045304 | II | Well tolerated | (62) | |
| Iniparib | PARP1 | Paclitaxel | NCT01204125 | II | Well tolerated | (62) | |
| Veliparib | PARP | Cyclophospharmide | NCT01306032 | II | Nausea and vomiting, decreased appetite, abdominal pain, diarrhea and malaise | (63) | |
| Talazoparib | PARP | AT13387 | NCT02627430 | I | Fatigue, anemia and thrombocytopenia | (64) | |
| Olaparib | PARP | NCT00679783 | II | Anemia, nausea, vomiting, fatigue, headache and cough | (65) | ||
| Veliparib | PARP | Cisplatin | NCT02595905 | II | Nausea and vomiting, decreased appetite, abdominal pain, diarrhea and malaise | (63) | |
| Olaparib | PARP | Radiotherapy | NCT02227082 | I | Anemia, nausea, vomiting, fatigue, headache and cough | (65) | |
| Olaparib | PARP | Paclitaxel, carboplatin | NCT00516724 | I | Anemia, nausea, vomiting, fatigue, headache and cough | (65) | |
| Talazoparib | PARP | NCT02401347 | II | Fatigue, anemia and thrombocytopenia | (64) | ||
| PD-1 | PDR001 | PD-1 | NCT02404441 | I/II | – | ||
| Pembrolizumab | PD-1 | PLX3397 (CSF1) | NCT02452424 | I/II | Arthralgia, fatigue, myalgia and nausea | (66) | |
| Pembrolizumab | PD-1 | Nab-paclitaxel, anthracycline, cyclophosphamide, carboplatin | NCT02622074 | I | Arthralgia, fatigue, myalgia and nausea | (66) | |
| Pembrolizumab | PD-1 | Compared with capecitabine, eribulin, gemcitaine and vinorelbine | NCT02555657 | III | Arthralgia, fatigue, myalgia and nausea | (66) | |
| Pembrolizumab | PD-1 | NCT02447003 | II | Arthralgia, fatigue, myalgia and nausea | (66) | ||
| Durvalumab | PD-1 | Paclitaxel | NCT02628132 | I/II | low grade skin and gastrointestinal tract which were well-tolerated | (67) | |
| Pembrolizumab | PD-1 | Niraparib | NCT02657889 | I/II | Arthralgia, fatigue, myalgia and nausea | (66) | |
| Pembrolizumab | PD-1 | INCB039110 (JAKi)/INCB050465 (PI3Ki) | NCT02646748 | I | Arthralgia, fatigue, myalgia and nausea | (66) |
EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; PARP, poly(ADP-ribose) polymerase; i, inhibitor; mA, monoclonal antibody; VEGFR, vascular endothelial growth factor receptor; HGFR, hepatocyte growth factor receptor; RTK, receptor tyrosine kinase; MET, mitogen-activated protein kinase kinase 1; FGFR, fibroblast growth factor receptor; PDGFR, platelet-derived growth factor receptor; PI3K, phosphoinositide 3-kinase; mTOR, mechanistic target of rapamycin; PIK3CA, phosphoinositide 3-kinase catalytic subunit α; AR, androgen receptor; PD-1, programmed death-1; CSF1, colony stimulating factor 1; JAK1, Janus kinase 1.