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

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.