Kidney cancer can be treated surgically in its early stages. However, its early symptoms may not be obvious, and about 25% to 30% of patients are already in advanced stages of the disease when they are seen, and a significant percentage of those treated early will experience recurrence. As the disease progresses, advanced kidney cancer can have a serious impact on survival time and quality of life.
Initially, cytokine therapies (interleukin-2, interferon-alpha, etc.) administered for advanced kidney cancer were ineffective and had serious toxic side effects. This was followed by the introduction of targeted drugs, which led to the era of tyrosine kinase inhibitors (TKI). The latest TKI drug, cabozantinib, is a milestone breakthrough in terms of efficacy.
Why does cabozantinib treat kidney cancer?
Cabotinib is a multipotent tyrosine kinase inhibitor (TKI) that blocks the biology of more than a dozen other target molecules, including AXL and MET, in addition to inhibiting 3 vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3). Compared to TKI’s that target the VEGF pathway alone, cabozantinib is able to more comprehensively and potently inhibit the pro-angiogenic mechanisms at the site of kidney cancer, cutting off the supply of oxygen and nutrients that cancer cells need to divide and proliferate.
Approval of Cabozantinib
Recently, cabozantinib has been approved in Europe and the United States for the clinical treatment of patients with all types of advanced kidney cancer:
- First-line regimens: first-line patients, especially those with intermediate or high-risk prognosis;
- Second-line regimens: follow-up therapy for patients who have failed first-line VEGF-targeted drug therapy.
In mainland China, cabozantinib is not yet available, and there are no announced plans to conduct studies related to kidney cancer treatment.
How is cabozantinib given?
Current clinical recommended dose: 60 mg of cabozantinib once daily on an empty stomach, 1 hour before or 2 hours after a meal.
How does cabozantinib work for kidney cancer?
As shown in Table 1, the clinical phase 2 CABOSUN study enrolled 157 patients with intermediate-to-high prognostic risk for primary treatment of advanced kidney cancer, and cabozantinib had a significant advantage as first-line therapy compared with the conventional regimen of sunitinib, both in terms of objective remission rate (20% vs 9%) and overall survival (26.6 vs 21.2 months).
Another clinical phase 3 METEOR study enrolled 658 patients with advanced metastatic kidney cancer who had received at least one prior TKI, with cabozantinib as second-line therapy, and showed overall superiority over everolimus in all efficacy measures (objective remission rate, overall survival, and progression-free survival), with particular clinical benefit in patients with bone metastases.
Table 1. Efficacy of first- and second-line cabozantinib for advanced kidney cancer compared with conventional regimens
| Medication grouping | Progression-free survival (months) | Overall survival (months) | Objective remission rate |
| Clinical phase 2 CABOSUN study: first-line treatment for patients with intermediate-to-high-risk advanced kidney cancer | |||
| Carbolitinib | 8.6 | 26.6 | 20% |
| Sunitinib | 5.3 | 21.2 | 9% |
| Clinical phase 3 METEOR study: second-line therapy after TKI treatment failure | |||
| Cabozantinib | 7.4 | 21.4 | 17% |
| Everolimus | 3.9 | 16.5 | 3% |
What are the side effects of Cabozantinib?
The most common serious adverse reactions to cabozantinib include hypertension, hand-foot syndrome, fatigue, anemia, and various gastrointestinal symptoms such as diarrhea, nausea, vomiting, abdominal pain, and loss of appetite.
Female patients should be careful with contraception and are prohibited from breastfeeding while taking the drug.
Summary
The effectiveness of cabozantinib in the treatment of advanced kidney cancer is highly recognized by national authorities worldwide, and its clinical status is gradually increasing, and it may become the routine drug of choice for patients with all types of kidney cancer in the future.
For Chinese patients, even if the original drug is available, it may be difficult to afford its high price, and the domestic generics under development may offer a better price/performance ratio.