Risk of selected gastrointestinal toxicities in metastatic renal cell carcinoma patients treated with immuno-TKI combinations: a meta-analysis

ABSTRACT

Objective

Recent years have registered the advent of novel treatment options for metastatic renal cell carcinoma (mRCC), including combination therapies with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Immuno-TKI combinations have been suggested to improve clinical outcomes but may also result in increased toxicity, including gastrointestinal (GI) adverse events.

Methods

Herein, we performed a meta-analysis aimed at comparing the risk of certain GI toxicities in mRCC patients treated with immuno-TKI combinations versus sunitinib monotherapy. Overall, four phase III trials (KEYNOTE-426, JAVELIN Renal 101, CheckMate 9ER, CLEAR) involving 3059 mRCC patients were available.

Results

The meta-analysis suggested an increased risk of all-grade diarrhea, grade 3–4 diarrhea and grade 3–4 decreased appetite in patients treated with immuno-TKI combinations. Conversely, an apparently higher risk of all-grade nausea was observed in the sunitinib group.

Conclusion

The meta-analysis suggested that immuno-TKI combinations are associated with higher risk of GI toxicities compared with sunitinib. Beyond the efficacy of immuno-TKI combinations in mRCC patients, careful consideration should be given to treatment-related adverse events, including GI toxicities. Early recognition and treatment are critical to maximize recovery.

KEYWORDS:

• Renal cell carcinoma
• immunotherapy
• immuno-tki combinations
• diarrhea
• tyrosine kinase inhibitors
• gastrointestinal toxicities

Article highlights

• Recent years have witnessed the advent of novel treatment options for metastatic renal cell carcinoma (mRCC), including combinations of an immune checkpoint inhibitor (ICI) and a tyrosine kinase inhibitor (TKI).

• As these combination therapies have now entered into routine clinical practice, a growing number of mRCC patients will be treated with immuno-TKI combinations.

• At the same time, concerns increase regarding treatment-related adverse events, including gastrointestinal (GI) toxicities.

• Herein, we performed a meta-analysis aimed at evaluating the risk of GI toxicities in mRCC patients treated with immuno-TKI combinations versus sunitinib monotherapy, highlighting that these combination therapies are associated with a higher risk of certain treatment-related GI adverse events.

• Beyond the unquestionable efficacy of immuno-TKI combinations, careful consideration should be given to treatment-related adverse events, including GI toxicities.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.