Immuno-oncology for renal cell carcinoma treatment: future perspectives for combinations and sequences with molecularly targeted agents

ABSTRACT

Introduction: From a theoretical viewpoint, combining molecularly targeted agents endowed with antiangiogenic properties with immunotherapy makes sense in treatment of metastatic renal cell carcinoma (RCC); this neoplasm is highly angiogenesis-dependent, as well as potentially immunogenic.

Areas covered: The authors performed a literature search looking for clinical trials aimed at evaluating efficacy and tolerability of combinations (or sequences) of molecularly targeted agents and different immunotherapeutic approaches in metastatic RCC.

Expert opinion: Combinations of molecularly targeted agents with old immunotherapeutics (i.e., cytokines) seem to add little to the presently available treatment standards (mainly monotherapy with targeted agents). Newer combinations with immune checkpoint inhibitors are promising but cumulative toxicity is an important issue, although highly dependent on the different companion drugs. Combinations with vaccines are ongoing, but first available data are not encouraging. A more thorough comprehension of the complex effects of these combinations on the immune system is mandatory to develop less empiric treatments.

KEYWORDS:

• Checkpoint inhibitors
• combinations
• cytokines
• immunotherapy
• molecularly targeted agents
• vaccines

Article highlights

• Combining molecularly targeted agents with immunotherapy makes sense in metastatic RCC due to its biological characteristics.

• Combinations of molecularly targeted agents with cytokines seem to add little to presently available treatment standards.

• Newer combinations with immune checkpoint inhibitors are promising but cumulative toxicity is an issue.

• What to give after nivolumab within a sequential treatment is another unresolved issue.

• As far as combinations of targeted agents with vaccines, first available data are not encouraging, but another large study is ongoing with intriguing preliminary data.

• A more thorough comprehension of the complex effects on the immune system of all the agents used in RCC, alone or in combination, is mandatory to develop less empiric combinations.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript has not been funded.