Treatment of advanced kidney cancer (renal cell carcinoma) is very tricky, and surgery and radiation therapy cannot cure it. The vast majority of kidney cancers are clear cell cancers, for which chemotherapy is also largely ineffective, and targeted drugs are now used primarily. If targeted therapy is not effective, the use of new immunotherapy drugs such as immune checkpoint inhibitors can enable some patients to extend their survival.
Overall, therapeutic agents for advanced kidney cancer can be divided into the following categories:
Targeted agents: widely used as first- and second-line therapy for advanced kidney cancer
Targeted drugs for kidney cancer that have been approved by the U.S. Food and Drug Administration (FDA) include:
- 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.
In recent years, domestic and international studies have shown that molecularly targeted drugs can significantly improve response rates and prolong survival in patients with advanced metastatic kidney cancer compared with traditional cytokine therapy. Therefore, since 2006, authoritative guidelines such as the National Comprehensive Cancer Network (NCCN) and the European Association of Urology (EAU) have included molecularly targeted therapeutics – sorafenib, sunitranib, and sulforaphane – in the list of drugs that can be used to treat metastatic kidney cancer. -sorafenib, sunitinib, tesirimus, bevacizumab in combination with interferon-alpha, pazopanib, everolimus, and axitinib as first- and second-line therapeutic agents for metastatic kidney cancer.
Cytokines: traditional first-line treatment options, less effective than targeted drugs
Mid- and high-dose interferon-alpha (IFN-α) and interleukin-2 (IL-2) have been the standard first-line treatment options for metastatic kidney cancer since the 1990s. However, the efficiency of cytokine therapy is only 5%~27%, and the median progression-free survival (PFS) is only 3~5 months, so most patients with metastatic kidney cancer cannot obtain satisfactory results. In the era of targeted agents, their first-line treatment status has been gradually replaced.
But because these drugs are relatively inexpensive, reimbursable by Medicare, and have easily controlled toxicities, they can still be the first choice for some kidney cancer patients who cannot afford the high cost of targeted drugs. In addition, some patients who are contraindicated to targeted therapy or have failed targeted therapy may also choose cytokine therapy.
Chemotherapy: only for some specific types of kidney cancer
Kidney cancer is more resistant to chemotherapy drugs, so chemotherapy is not usually preferred for advanced kidney cancer. However, chemotherapy can be given to patients with some specific types of kidney cancer, such as non-clear cell carcinoma, or clear cell carcinoma with significant sarcomatoid changes.
The main chemotherapy drugs used to treat advanced metastatic kidney cancer are gemcitabine, fluorouracil or capecitabine, and cisplatin.
New immunotherapy: new hope for prolonging survival in patients with advanced kidney cancer
Immunotherapy has come to the forefront in recent years and has created a new revolution in the treatment of advanced tumors. The immune checkpoint inhibitor class of drugs has shown promising results in a variety of tumors.
Nivolumab (also known as nabulizumab, O drug) was the first immunotherapy drug approved by the FDA for advanced kidney cancer, and it works by blocking the binding of programmed death protein-1 (PD-1) to programmed death ligand-1 (PD- L1), allowing immune-tolerant T cells to reactivate and engage in killing tumor cells.
A randomized phase 3 clinical trial showed that in patients with advanced kidney cancer who had been treated with one to two tumor vascular targeting drugs, treatment with nabumab resulted in longer survival and a lower incidence of serious adverse events compared with the targeted drug everolimus.
Another pivotal clinical trial (CheckMate 016) showed that in patients with intermediate-to-high-risk advanced kidney cancer, the combination of nabumab and another immune checkpoint inhibitor, ipilimumab, a CTLA-4 antibody, resulted in longer survival than sunitinib longer survival times than treatment with sunitinib. As a result, the FDA approved the combination of these two immunotherapy drugs in 2018 as an initial treatment option for advanced kidney cancer.
Navumab is currently available in China but has not yet been approved for kidney cancer, and ipilimumab is not yet available in China. It is believed that more and more Chinese patients will benefit from these new drugs in the near future.