For limited kidney cancer (i.e., the tumor is confined to the kidney and has not yet metastasized), surgery is the treatment of choice. However, when kidney cancer is advanced (metastatic kidney cancer), surgery is of limited therapeutic value and targeted drugs are now used primarily to prolong patient survival.
Why are targeted drugs able to treat advanced kidney cancer?
If you compare chemotherapy to a “bomb” that kills both tumors and normal tissue, it does not discriminate between friend and foe. The tumor-targeted therapy is like a “biological missile” that enters the body and specifically binds to cancer-causing targets at the molecular level to inhibit tumor growth and reduce damage to normal tissues, making it a highly effective and less toxic treatment.
Targeted therapeutics can also be divided into several categories depending on the mechanism of action, and the target molecule or protein they target must play a critical role in the growth and proliferation of tumor cells.
75% to 85% of renal cell carcinomas are enriched with tumor vasculature and have many growth factor receptors overexpressed on the tumor cell surface, including VEGFR (vascular endothelial growth factor receptor), PDGFR (platelet-derived growth factor receptor), and FGFR (fibroblastogenic factor receptor), and these overexpressed receptors can stimulate tumor cell growth or stimulate These overexpressed receptors can stimulate the growth of tumor cells or stimulate the growth of neovascularization inside the tumor, leading to the proliferation of the tumor, and these are useful targets. The current targeted therapy for kidney cancer is aimed at these targets, preventing tumor neovascularization, thereby cutting off the tumor’s nutrient supply and “starving” the tumor.
What are the targeted drugs for advanced kidney cancer?
What are the targeted drugs for advanced kidney cancer?
There are several FDA-approved targeted drugs for the treatment of advanced kidney cancer:
- Sunitinib (Sunitinib)
- Sorafenib (Sorafenib)
- Pazopanib (Pazopanib)
- Axitinib (Axitinib)
- Everolimus (Everolimus)
- Tesilimus (Temsirolimus)
- Bevacizumab (Bevacizumab)
- Cabozantinib (Cabozantinib)
- Levatinib (Lenvatinib)
And the main drugs currently available in China are sunitinib, sorafenib, pegaptanib, axitinib, and everolimus.
Sorafenib
Sorafenib is a small-molecule multi-targeted tyrosine kinase inhibitor that acts on both tumor cells and tumor blood vessels, and was approved by the FDA in 2005 as a first-line agent for the treatment of advanced kidney cancer.
An earlier clinical trial in Chinese patients with advanced kidney cancer showed that 84% of patients treated with sorafenib achieved disease control with a median disease-free survival of 9.6 months.
Recent clinical studies in China have shown that increasing the dose or combining interferon-alpha can improve the efficiency of sorafenib in the treatment of advanced kidney cancer, but with a corresponding increase in adverse effects.
Sunitinib
Sunitinib and sorafenib are both small-molecule multi-target tyrosine kinase inhibitors with slightly different targets, but both have dual anti-angiogenic and anti-tumor effects.
Foreign studies have shown that sunitinib approximately doubled overall survival (28.1 months vs 14.1 months) and was significantly more effective (47% vs 12%) in patients with advanced kidney cancer compared with interferon-alpha.
A clinical study of patients with advanced kidney cancer in China showed a median disease-free survival of 14.2 months, a median overall survival of 30.7 months, and an overall efficacy rate of 30.7%, with most adverse events being mild to moderate, with sunitinib treatment.
Everolimus
The protein that everolimus inhibits is called “m-TOR” and is closely associated with both tumor cell proliferation and neovascularization. When m-TOR is blocked, neovascularization is reduced, tumor cells may stop dividing, and spontaneous apoptosis may occur. Everolimus was approved by the FDA in 2009 as a second-line treatment option for patients with advanced kidney cancer after failure of sorafenib and sunitinib therapy.
In an international clinical trial, treatment with everolimus extended median disease-free survival by about 3 months compared with placebo in patients with metastatic kidney cancer who had failed treatment with sorafenib and/or sunitinib, with a median overall survival of 14.8 months.
A multicenter clinical study of domestic patients showed that second-line treatment with everolimus resulted in a median disease-free survival of 6.9 months and a one-year survival rate of 56%. A study in Taiwan showed that second-line treatment with everolimus resulted in a median overall survival of 20.7 months.
In addition, second-line use of everolimus was effective regardless of the patient’s first-line treatment with sorafenib and sunitinib.
Axitinib
Axitinib is an oral, potent and highly selective tyrosine kinase inhibitor that acts on vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3 to inhibit angiogenesis and tumor progression. Approved in China, it is mainly used in adult patients with progressive kidney cancer who have failed previous cytokine-related treatment regimens (interleukin-2, interferon-alpha, etc.); it can also be used in patients with advanced kidney cancer who have failed or are intolerant to previous anti-angiogenic therapeutic agents.
An international multicenter study showed that axitinib treatment of patients with metastatic kidney cancer who failed first-line therapy resulted in a disease-progression-free survival of 6.7 months and a 19% efficiency rate.
In a clinical trial of Asian patients with advanced kidney cancer, axitinib was associated with a disease-free survival of 6.5 months and a 23.7% efficiency rate. In addition, disease progression-free survival was 10.1 months with axitinib in patients previously treated with cytokines, compared with 4.7 months with sunitinib in patients previously treated with axitinib. This suggests that patients who received prior cytokine therapy are more likely to benefit from axitinib therapy.
Summary
Because targeted agents are effective in prolonging survival in patients with advanced kidney cancer, the National Comprehensive Cancer Network (NCCN), the European Association of Urology (EAU), and other Since 2006, the National Comprehensive Cancer Network (NCCN), European Association of Urology (EAU) and other authoritative guidelines have included molecularly targeted therapies – sorafenib, sunitinib, tesirimus, bevacizumab in combination with interferon-alpha, pazopanib, everolimus and axitinib – as first- and second-line therapeutic agents for metastatic kidney cancer.