The early stages of kidney cancer are best treated with surgical resection, with a 5-year survival rate of more than 90%. However, once the disease progresses to advanced stages, the 5-year survival rate dives dramatically, with only 11.7% of those with distant metastases. In the past decade, the treatment of advanced kidney cancer has improved significantly with the introduction of several tyrosine kinase inhibitors (TKI) into the clinic. Among these, axitinib single-agent regimens have been approved for second-line treatment, and multiple trials are underway to continue to explore additional applications in kidney cancer.
Why can axitinib treat kidney cancer?
Axitinib is a selective, potent tyrosine kinase inhibitor (TKI) that targets 3 vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, and VEGFR-3) to inhibit their pro-angiogenic mechanisms, thereby blocking the blood supply to kidney cancer, making it difficult for cancer cells to get the oxygen and nutrients they need to divide and proliferate, and halting their continued progression.
Approval of axitinib
Axitinib has been approved in more than 80 countries, including China, for patients with advanced kidney cancer who have failed prior treatment with a TKI or cytokine.
How is axitinib given?
Current clinical recommended dose: 5 mg of axitinib orally twice daily; the interval between doses is about 12 hours.
How well does axitinib work for kidney cancer?
As shown in Table 1, the global clinical phase 3 AXIS study showed that second-line treatment with axitinib was more beneficial than sorafenib in improving remission rates (19.4% vs 9.4%) and inhibiting progression.
A total of 204 patients with advanced kidney cancer who failed first-line therapy were enrolled in the Asian registry study, including 188 Chinese patients. Statistics showed that axitinib as a second-line regimen significantly improved the objective remission rate compared with sorafenib (21.8% vs 9.4%).
However, axitinib did not significantly extend overall survival in either the international or Chinese study.
Table 1. Efficacy of Axitinib vs Sorafenib in Second-Line Treatment of Advanced Kidney Cancer
| Medication grouping | Progression-free survival (months) | Overall survival (months) | Objective remission rate |
| International Clinical Phase 3 AXIS Study | |||
| Axitinib | 6.8 | 20.1 | 19.4% |
| Sorafenib | 4.7 | 19.2 | 9.4% |
| Registration Study in Asia | |||
| Axitinib | 6.4 | 17.2 | 21.8% |
| Sorafenib | 4.6 | 18.1 | 9.4% |
Can axitinib be used as a first-line agent?
The clinical phase 3 AGILE study showed that axitinib alone in first-line treatment of advanced kidney cancer was similar to, but not significantly superior to, sorafenib. As treatment concepts have evolved, it is now believed that combining drugs with different anti-cancer mechanisms is needed to better improve outcomes.
A number of studies exist that are attempting to combine axitinib with immune checkpoint inhibitors (eg, pablizumab, avelumab) as a first-line regimen to assess whether it can help improve clinical outcomes in patients with primary treatment of advanced kidney cancer. If successful, it will certainly change the current conventional strategy and enable a newer generation of first-line treatment for advanced kidney cancer.
What are the common adverse effects of axitinib?
The most common serious adverse reactions to axitinib include hypertension, hand-foot syndrome, fatigue, and various gastrointestinal symptoms such as diarrhea, nausea, vomiting, abdominal pain, and loss of appetite.
Female patients should be advised to use contraception and are prohibited from breastfeeding while taking the drug.
Summary
Axitinib is available in China and approved for second-line treatment of advanced kidney cancer. However, more compelling are the clinical studies of axitinib in combination with immune checkpoint inhibitors as a first-line regimen, which is important to further improve the overall outcome and prolong patient survival in advanced kidney cancer.