Table 3.
Basis for RP2D and important toxicities of FDA approved MTAs in solid tumors.
| Drug | Basis for RP2D | Select adverse events |
|---|---|---|
| Imatinib | PK/PD | Rash, edema, decreased LVEF, myelosuppression, myalgias and arthralgias |
| Trastuzumab | PK | Cardiomyopathy, asthenia, fever, chills |
| Pertuzumab | PK | Diarrhea, fatigue, nausea, anemia |
| Lapatinib | Toxicity + efficacy | Decreased LVEF, rash, hand‐foot syndrome, diarrhea, elevated LFTs. |
| Erlotinib | Toxicity | Acneiform rash, diarrhea, interstitial lung disease |
| Gefitinib | PK + efficacy | Acneiform rash, diarrhea, interstitial lung disease |
| Cetuximab | PK | Acneiform rash, nail changes, diarrhea, hypomagnesemia, interstitial lung disease |
| Panitumumab | PK/PD | Acneiform rash, diarrhea, hypomagnesemia, hypocalcaemia, interstitial lung disease |
| Temsirolimus | Efficacy | Emesis, myelosuppression, dyslipidemia, diarrhea, rash and nephrotoxicity |
| Everolimus | PK/PD | Mucositis, rash, electrolyte abnormalities, dyslipidemia, diarrhea, pneumonitis, peripheral edema |
| Vemurafenib | Toxicity | Arthralgias, rash, squamous cell ca, keratocanthomas |
| Crizotinib | Toxicity | Nausea, vomiting, diarrhea, hepatotoxicity |
| Aflibercept | Toxicity + PK | Neutropenia, diarrhea, hypertension, eye irritation or visual disturbance |
| Bevacizumab | PK | Hypertension, thromboembolism, gastrointestinal perforation, poor wound healing |
| Sorafenib | Toxicity | Hypertension, rash, hand‐foot syndrome, diarrhea, emesis, myelosuppression, delayed wound healing, hypophosphatemia |
| Sunitinib | Toxicity | Hypertension, emesis, myelosuppression, hypothyroidism, adrenal dysfunction, decreased LVEF, yellow skin discolouration and mucositis |
| Pazopanib | PK/PD + efficacy | Fatigue, increased LFTs, diarrhea, hypothyroidism |
| Regorafenib | Toxicity + PK/PD | Hypertension, hand foot syndrome and diarrhea |
| Cabazantinib | Toxicity + efficacy | Hand foot syndrome and mucositis |
| Vandetanib | Toxicity and PK | QTc prolongation, diarrhea, asthenia and fatigue |
| Ipilimumab | Efficacy | Autoimmune colitis, dermatitis and hepatitis. Various endocrinopathies. |
| Enzalutamide | Toxicity | Fatigue, diarrhea, flushing, edema |
| Axitinib | Toxicity | Diarrhea, hypertension, weight decrease, anorexia |
| Vismodegib | PK | Muscle spasms, alopecia, dysgeusia, weight loss, fatigue |
LFTs, liver function tests; LVEF, left ventricular ejection fraction; PK, pharmacokinetic; PD, pharmacodynamic.