Targeted agents for advanced kidney cancer have emerged in recent years, presenting both opportunities and challenges. In addition to the efficacy, side effects, and risk level of tumor pathology type, the selection of targeted drugs should be considered in conjunction with the patient’s comorbidities. In order to achieve efficacy while minimizing the impact of side effects on patients’ quality of life, individualization of treatment and maximization of patient benefit can be achieved.
In addition, economic factors are an inescapable problem in targeted therapy for advanced kidney cancer, but it is believed that as targeted drugs such as sunitinib and axitinib enter the national health insurance list, prices will drop significantly in the future, easing the economic burden of drug use and benefiting more patients with advanced kidney cancer.
Targeted drugs for kidney cancer come in two categories:
- A class of anti-angiogenic tyrosine kinase inhibitor (TKI). Clear cell renal cancer has a VHL gene mutation (36% mutation frequency), which causes tumor cells to produce a lot of VEGF protein, and the excess of VEGF increases angiogenesis; some TKI drugs control tumor neo-vascularization by blocking VEGF. some TKI drugs control the formation of new blood vessels in tumors by blocking VEGF.
- There is also the mammalian target of rapamycin (mTOR) inhibitor, which is an intracellular kinase that regulates the expression of cell growth, survival, and angiogenesis-related proteins that induce tumor cell proliferation, growth, and metabolism. mTOR inhibitors work by blocking mTOR to exert anti-tumor effects.
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U.S. Food and Drug Administration (FDA)-approved targeted drugs for kidney cancer
| R&D Company | Drug target | Target drug name | Time to market | Marketing status in China |
| Eisai | VEGFR | lenvatinib (levatinib) | 2015 | Marketed in 2018, not yet covered by Medicare |
| Novartis | mTOR | everolimus (everolimus) | 2009 | Launched in 2013, Class B Medicare |
| Wyeth | mTOR | temsirolimus (tesilimus) | 2007 | Not available |
| Pfizer | PDGFRα/β, VEGFR1/2/3, KIT, FLT3, RET | sunitinib (sunitinib) | 2006 | launched in 2007, Class B Medicare |
| Bayer | VEGFR1/2/3, PDGFR-β, B-raf, KIT, RET, C-Raf, FLT3 | sorafenib tosylate (sorafenib) | 2005 | Launched in 2009, the first molecularly targeted drug for kidney cancer in China, Class B medical insurance |
| Genentech | VEGF | bevacizumab (bevacizumab) | 2004 | launched in 2010, Class B Medicare |
| GlaxoSmithKline | VEGFR, PDGFR, KIT | pazopanib (pazopanib) | 2009 | launched in 2017, Class B Medicare |
| Pfizer | KIT, PDGFRβ, VEGFR1/2/3 | axitinib (axitinib) | 2012 | launched in 2015, Class B Medicare |
| Takeda | FLT3, KIT, MET, RET, VEGFR2 | cabozantinib (cabozantinib) | 2011 | Not available |
Among the targeted drugs for kidney cancer that have been marketed in China, sorafenib, sunitinib, and pazopanib are first-line treatment options, with sorafenib and sunitinib being the most widely used. If first-line treatment fails, second-line treatment drugs such as everolimus and axitinib can be chosen.
Before choosing targeted drug therapy, one should also understand the toxic side effects that each drug can cause. In general, targeted drugs with similar mechanisms of action have almost the same adverse effects. Common adverse reactions to targeted drugs for kidney cancer include:
- Hand-foot syndrome
- Stomatitis
- High blood pressure
- Loss of body weight
- Diarrhea
- Decreased white blood cells
- Decreased platelets
- hypothyroidism
- Rash
- Liver function abnormalities
- Depigmentation of skin and hair
These adverse reactions are generally mild to moderate and can be tolerated by most patients, and even if serious adverse reactions occur, they can be resolved with drug dose adjustment and symptomatic management. Therefore, before treatment with targeted drugs, you should consult with your doctor about possible adverse reactions, and your doctor will choose the right drug for your specific condition:
- Sunitinib should be used with caution in patients with the following conditions.
- thyroidal dysfunction;
- Significantly decreased left ventricular ejection fraction (LVEF);
- Significantly decreased left ventricular ejection fraction (LVEF)
- Chronic heart disease (chronic heart failure, coronary artery disease, etc.);
- Severe uncontrolled hypertension.
- High incidence of hand-foot skin reactions and gastrointestinal toxic side effects caused by sorafenib, not for patients with chronic gastrointestinal disease.
- Everolimus should be used with caution in patients with poor lung function, pneumonia, or other active infections.
There are currently no effective biomarkers for targeted therapy in kidney cancer, but patients can be finely stratified according to the disease itself. For some patients with slow-growing tumors, an active surveillance strategy can be used, whereas for tumors with a large tumor load and rapid growth, targeted drug therapy needs to be given promptly.