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Introduction

Over the last 2 decades, tyrosine kinase inhibitors (TKIs) have emerged as an important treatment option for patients with cancer. Activated tyrosine kinase receptors (including vascular endothelial growth factor receptor [VEGFR], epidermal growth factor receptor [EGFR], and platelet-derived growth factor receptor [PDGFR]) cause the cell to stay “on” by allowing continued cellular signaling, which is important in tumor transformation, cell growth, proliferation, and angiogenesis.¹ Although more than 2 dozen TKIs have now been approved for the treatment of patients with a variety of cancer types, patients with advanced disease often become resistant to treatment and eventually exhibit disease progression.^1-2 As a result, a great deal of recent research has focused on the identification of new treatment strategies for patients with advanced disease in both the first-line setting and for those with disease progression who’ve received prior therapy. Solid tumors for which TKIs have recently received US Food and Drug Administration (FDA) approval for new or expanded indications include the following:

• Renal cell carcinoma (RCC): Kidney cancer accounts for an estimated 62 700 new cancer cases in the United States (US) in 2016 and an estimated 14 240 deaths.³ RCC also accounts for more than 90% of kidney cancers and of those the majority subtype is clear cell carcinoma. RCC is often diagnosed in early stages where the overall 5-year survival rate is more than 90% with current treatment options. However, the 5-year survival rate for those with metastatic disease is much worse at approximately 12%.⁴
  
  
• Gastrointestinal stromal tumors (GIST): GISTs are a subtype of sarcomas which is a heterogeneous group of rare solid tumors that may involve bone or soft tissues. In the US, GIST is thought to account for an estimated 5000 new cancer cases each year, occurring primarily in the stomach or small intestine.^5-6 The overall 3-year survival is approximately 55% in patients with metastatic GIST.⁶ Chemotherapy is generally not effective for patients with GIST and surgical resection is the treatment of choice where possible.⁵ However, many patients have unresectable or metastatic disease, and recurrence after resection may occur in as many as 40% of patients in the 2 years after surgery.⁷
  
  
• Differentiated thyroid cancer (DTC): Approximately 62 450 patients are estimated to be diagnosed with thyroid cancer in 2016, and an estimated 1980 will die from this disease. DTC, which includes papillary, follicular, and Hűrthle cell carcinoma, accounts for more than 90% of these cases. ^8,-9 Thyroid cancer is the most rapidly increasing cancer type in the US, with women accounting for approximately 80% of cases.³ The 5-year survival rate is approximately 98% of patients with nonmetastatic thyroid cancer overall, and approximately 54% for those with distant metastases.^3,8

Pharmacists are essential members of the interdisciplinary healthcare team, particularly in the oncology setting, and can help direct the safe and effective use of oral cancer therapies, which require careful attention to appropriate treatment selection, preventing and managing adverse events (AEs), and ensuring that patients are adherent to therapy. This activity provides an update and overview of recently approved new TKIs and new approvals of existing TKIs for the treatment of patients with solid tumors, including RCC, DTC, and GIST. TKIs have also recently been approved for patients with non-small cell lung cancer, including osimertinib and alectinib. The use of these agents requires molecular and genetic testing for tumor markers that are associated with susceptibility or resistance to targeted treatment, which is beyond the scope of this activity.