Table 3.
Details of reported treatment-related AEs following the administration of PI3K/Akt/mTOR inhibitors in lung cancer cases.
| Phase | Treatment-related AEs * | Any grade AEs * | High frequent treatment-related AEs | Trial identifier | ||||
|---|---|---|---|---|---|---|---|---|
| Any G. | ≥ Grade 3 | Serious | Dis-cont. | Any grade | ≥ Grade 3 | |||
| PI3K inhibitors | ||||||||
| GDC-0941+Erlotinib | I | 100 | 66.7 | 33.3 | 19.3 | Diarrhea, Nausea, Fatigue | Rash, Elevated ALT | NCT00975182 |
| GDC-0941+Paclitaxel+ Carboplatin+/-Bevacizumab | I | 100 | 86.4 | 84.8 | 33.3 | Nausea, Vomiting, Fatigue | Neutropenia, Dyspnea, Anemia | NCT00974584 |
| BKM120 | II | NA | NA | NA | NA | Hyperglycemia, Pruritus, Diarrhea | Hyperglycemia, Asthenia, Increased ALT | NCT01820325 |
| BKM120+MEK162 | Ib | 93.3 | 64 | NA | 29.2 | Increased CPK, Diarrhea, Increased AST | Increased CPK, Increased ALT, Increased AST | NCT01363232 |
| BKM120+Trametinib | Ib | 97 | 65 | 19 | 31 | Dermatitis acneiform, Diarrhea | Increased CPK, Increased ALT, Stomatitis | NCT01155453 |
| BKM120+Everolimus | I | NA | NA | NA | NA | Hyperglycemia, Increased AST/ALT | Fatigue, Hypokalemia, Pneumonia | NCT01470209 |
| XL147 | I | 63.8 | 13 | 4.3 | 2.9 | Skin toxicities, Nausea, Diarrhea | Rash, Diarrhea | NCT00486135 |
| PX-866+Docetaxel | II | NA | NA | NA | NA | Diarrhea, Nausea, Vomiting | Neutropenia | NCT01204099 |
| Akt inhibitors | ||||||||
| Perifosine+Radiotherapy | I | NA | NA | NA | NA | Nausea, Fatigue, Diarrhea | NA | [152] |
| MK-2206+Erlotinib | II | NA | 55 | NA | NA | NA | Rash, Diarrhea, Fatigue | NCT01294306 |
| MK-2206+AZD6244+Sorafenib | II | NA | NA | NA | NA | Fatigue, Diarrhea, Rash | Fatigue, Diarrhea, Rash | NCT01248247 |
| MK-2206+Gefitinib | I | NA | NA | NA | NA | Increased eosinophil, Rash, Diarrhea | NA | NCT01147211 |
| mTOR inhibitors | ||||||||
| Rapamycin+Pemetrexed | I/II | NA | NA | NA | NA | Lymphopenia, Anemia, Fatigue | Lymphopenia, Hypophosphatemia, Neutropenia | NCT00923273 |
| Rapamycin+Afatinib | Ib | 100 | 66.7 | 56.4 | 23.1 | Diarrhea, Mucosal inflammation, Rash | Diarrhea, Mucosal inflammation, Asthenia, Rash | NCT00993499 |
| Temsirolimus | II | NA | 64 | NA | NA | NA | Dyspnea, Fatigue, Hyperglycemia, Hypoxia, Nausea | [118] |
| Everolimus+Gefitinib | II | NA | 22.5 | 4.76 | 3.2 | Rash, Diarrhea, Oral ulcerations | Lymphopenia, Hyponatremia, Fatigue, Diarrhea | NCT00096486 |
| Everolimus+Erlotinib | II | 100 | 72.7 | NA | 10.6 | Diarrhea, Stomatitis, Rash | Stomatitis, Asthenia, Diarrhea | NCT00456833 |
| Ridaforolimus | I | NA | NA | NA | 0 | Mouth sores, Rash, Anemia | Mouth sores, Hyperglycemia, Thrombocytopenia | NCT00704054 |
| Dual PI3K/mTORs inhibitors | ||||||||
| NVP-BEZ235+Everolimus | Ib | NA | NA | 17.3 | NA | Fatigue, Anorexia, Nausea, Diarrhea | Increased AST, Increased ALP, Anemia | NCT01508104 |
| XL765+Erlotinib | I | 89.1 | 15 | 8.7 | 4.3 | Diarrhea, Rash, Nausea | Increased AST, Nausea, Vomiting | NCT00777699 |
AEs: Adverse events; Any G.: Any grade; ALT: Alanine aminotransferase; CPK: Creatine phosphokinase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; Dis-cont: Discontinued; NA: Not available.*: % of all patients.