TABLE 9.
Molecularly targeted agents being used or under consideration for pediatric cancers (adapted and updated from Chow et al., J Clin Oncol 2018)
| Target(s) | Drug(s) | Notable toxicities* |
|---|---|---|
| ALK/ROS | Ceritinib Crizotinib Ensartinib Lorlatinib |
Arrhythmia Dyslipidemia (lorlatinib) Hyperglycemia (ceritinib) Hallucinations / psychiatric (lorlatinib) Neuropathy/neuromuscular Pulmonary embolism (crizotinib) Respiratory Vision changes |
| BCR/ABL, KIT, PDGFR | Dasatinib Imatinib Nilotinib Ponatinib |
Cardiac dysfunction Edema, effusions Growth & stature* Pulmonary hypertension (dasatinib) Thyroid dysfunction Vascular events, including myocardial ischemia, peripheral arterial occlusion, and stroke (ponatinib) |
| BRAF | Dabrafenib Vemurafenib |
Hyperglycemia (dabrafenib) New acute development of skin cancers QT-prolongation (vemurafenib) Radiation sensitivity |
| CD3 | Blinatumomab | B cell aplasia (CAR T cells)* Cytokine release syndrome Neurotoxicity |
| CD19 | Blinatumomab Chimeric antigen receptor (CAR) T cells |
Same as with CD3-targeted agents above |
| CD20 | Rituximab | B cell aplasia |
| CD30 | Brentuximab vedotin | Neuropathy Progressive multifocal leukoencephalopathy |
| CD33 | Gemtuzumab ozogamicin | Hepatotoxicity, sinusoidal obstruction syndrome |
| CDK/cyclin (cell cycle) | Palbociclib Ribociclib |
QT-prolongation (ribociclib) |
| EZH2 | Tazemetostat | Limited experience to date |
| GD2 | Dinutuximab Hu3F8 Hu14.18K322A |
Capillary leak syndrome Neuropathic pain Reversible posterior leukoencephalopathy |
| HDAC (histone deacetylase) | Entinostat Fimepinostat Panobinostat Romidepsin Vorinostat |
Arrhythmia / myocardial infarction Pulmonary embolus (vorinostat) Limited experience for entinostat, fimepinostat |
| MEK/MAPK | Binimetinib Cobimetinib Selumetinib Trametinib |
Cardiac dysfunction Skin toxicity Vision changes, retinopathy |
| mTOR | Everolimus Sirolimus Temsirolimus ABI-009 (Nab-Rapamycin) LY3023414 |
Dyslipidemia Hyperglycemia |
| PD-1, PDL-1, CTL4 (immune checkpoint) | Atezolizumab Avelimumab Cemiplimab Durvalumab Ipilimumab Nivolumab Pembrolizumab |
Auto-immune/inflammatory, including: Endocrinopathies Myocarditis Neurotoxicity Pneumonitis |
| PI3K | Fimepinostat LY3023414 |
Hyperglycemia |
| TRK | Entrectinib Larotrectinib |
Limited experience to date |
| VEGF, VEGFR, PDGFR, RET | Axitinib Bevacizumab Cabozantinib Lenvantinib Pazopanib Sorafenib Vandetanib |
Cardiac dysfunction Hemorrhage, impaired wound healing Hepatotoxicity (pazopanib) Hypertension, proteinuria Intestinal perforation/fistula (bevacizumab) Thromboembolism Thyroid dysfunction (axitinib, pazopanib, sorafenib) |
*
Toxicities that may persist well after cessation of therapy, or develop later