What should I do after failing first-line treatment for advanced kidney cancer patients?

by Specialist

If detected, diagnosed, and treated early, most kidney cancer patients can survive long term. However, about 30% of patients are already at an advanced stage at the time of presentation. An additional 10% to 20% of patients treated early will have a recurrence.

Currently, common first-line treatment drugs for advanced kidney cancer in China include sunitinib, sorafenib, and pazopanib. In the past, there were almost no drugs available after failure of first-line treatment for advanced kidney cancer, and many new drugs have been introduced in recent years to break this dilemma.

Today, second-line drugs approved worldwide for advanced kidney cancer include:

  • Tyrosine kinase inhibitor (TKI): This is also known as a “targeted agent” that targets vascular endothelial growth factor (VEGF), which inhibits tumor neovascularization. ), which inhibits tumor neovascularization and causes tumors to “die of ischemia”. The most widely used drugs in this class include axitinib, lenvatinib, and cabozantinib, which has multiple targets in addition to VEGF.

  • Mammalian target of rapamycin, mTOR inhibitors: mTOR is an important regulator of cell growth and proliferation and is the target of this class of drugs, represented by everolimus.

    • .

  • Immune checkpoint inhibitors: Also known as “immunotherapies”, these drugs reignite the tumor-killing effect of the patient’s immune system by blocking the tumor cells’ PD-1 system that interferes with the body’s immunity. The main representative drug is nivolumab (O-Drug).

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Table 1. Major second-line agents for advanced kidney cancer and the population for which they are indicated

Lenvatinib + everolimus

Second-line dosing Approved indications in Europe and the US Applicable populations Method of administration
Everolimus

  • US: treatment failure with sunitinib or sorafenib;

  • Europe: failure of treatment with one prior VEGF-targeted agent.

  • Unsuitable for or intolerant of other second-line drugs

  • Need for dialysis

 Oral
Axitinib

  • US: treatment failure with sunitinib or sorafenib;

  • Europe: failure of treatment with one prior VEGF-targeted agent.

  • Poorly tolerated to other second-line drugs

  • Good prognosis

  • First-line treatment with interferon 

 Oral
Navulizumab

  • US: failure of one prior anti-angiogenic agent treatment;

  • Europe: failure of first-line therapy.

  • Age <65 years

  • Higher risk of tumor progression

  • with impaired renal function or need for dialysis 

 Intravenous infusion lasting at least 60 minutes

Cabozantinib (not yet available in this country)

  • U.S.: failure of one prior anti-angiogenic agent treatment;

  • Europe: Failure of one prior VEGF-targeted agent.

  • Age <65 years

  • Higher risk of tumor progression

  • with impaired renal function or need for dialysis 

 Oral on an empty stomach

  • US: failure of prior treatment with an antiangiogenic agent;

  • Europe: failure of one prior VEGF-targeted agent.

  • Severe disease or poor prognosis requiring intensive therapy

 Oral

Second-line options for advanced kidney cancer, how to choose?

How should these second-line drugs be chosen? The National Comprehensive Cancer Network (NCCN) has made the following recommendations for second-line treatment of advanced kidney cancer, with nabritumomab and cabozantinib as the drugs of choice for second-line treatment.

Table 2. NCCN-recommended second-line agents for advanced kidney cancer

Class 1

Class 2A

Recommendation Level Medications
Class 1 Preferred Navulizumab, Cabozantinib
Axitinib, lenvatinib + everolimus
Evimox

Note: A Class 1 recommendation is based on a higher level of evidence (e.g., randomized controlled clinical trials) and NCCN committee consensus. a Class 2A recommendation is based on a lower level of evidence and NCCN committee consensus. a Class 1 recommendation is stronger evidence and more informative.