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.

中文翻译：

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接受免疫-TKI 联合治疗的转移性肾细胞癌患者的特定胃肠道毒性风险：一项荟萃分析

摘要

客观的

近年来，转移性肾细胞癌 (mRCC) 出现了新的治疗选择，包括免疫检查点抑制剂 (ICI) 和酪氨酸激酶抑制剂 (TKI) 的联合治疗。已提出免疫-TKI 组合可改善临床结果，但也可能导致毒性增加，包括胃肠道 (GI) 不良事件。

方法

在此，我们进行了一项荟萃分析，旨在比较接受免疫 TKI 联合治疗与舒尼替尼单药治疗的 mRCC 患者的某些胃肠道毒性风险。总体而言，共有涉及 3059 名 mRCC 患者的四项 III 期试验（KEYNOTE-426、JAVELIN Renal 101、CheckMate 9ER、CLEAR）可用。

结果

荟萃分析表明，在接受免疫 TKI 联合治疗的患者中，全级腹泻、3-4 级腹泻和 3-4 级食欲下降的风险增加。相反，在舒尼替尼组中观察到明显更高的全级恶心风险。

结论

荟萃分析表明，与舒尼替尼相比，免疫-TKI 组合与更高的胃肠道毒性风险相关。除了免疫 TKI 组合对 mRCC 患者的疗效外，还应仔细考虑与治疗相关的不良事件，包括胃肠道毒性。早期识别和治疗对于最大限度地恢复至关重要。