Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have gained therapeutical significance in cancer therapy over the last years. Due to the high efficacy of each substance group, additive or complementary effects are considered, and combinations are the subject of multiple prospective trials in different tumor entities. The majority of available data results from clinical phase I and II trials. Although regarded as well-tolerated therapies ICI-TKI combinations have higher toxicities compared to monotherapies of one of the substance classes and some combinations were shown to be excessively toxic leading to discontinuation of trials. So far, ICI-TKI combinations with nivolumab + cabozantinib, pembrolizumab + axitinib, avelumab + axitinib, pembrolizumab + lenvatinib have been approved in advanced renal cell (RCC), with pembrolizumab + lenvatinib in endometrial carcinoma and with camrelizumab + rivoceranib in hepatocellular carcinoma (HCC). Several ICI-TKI combinations are currently investigated in phase I to III trials in various other cancer entities. Further, the optimal sequence of ICI-TKI combinations is an important subject of investigation, as cross-resistances between the substance classes were observed. This review reports on clinical trials with ICI-TKI combinations in different cancer entities, their efficacy and toxicity.

中文翻译：

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多多益善？免疫检查点抑制剂和酪氨酸激酶抑制剂组合治疗晚期实体癌的证据和功效

过去几年，免疫检查点抑制剂（ICI）和酪氨酸激酶抑制剂（TKI）在癌症治疗中取得了重要意义。由于每个物质组都具有高效能，因此考虑了附加或互补效应，并且组合是不同肿瘤实体中多项前瞻性试验的主题。大多数可用数据来自临床 I 期和 II 期试验。尽管被认为是耐受性良好的疗法，但 ICI-TKI 组合与其中一种物质的单一疗法相比具有更高的毒性，并且某些组合被证明毒性过高，导致试验终止。迄今为止，ICI-TKI联合纳武单抗+卡博替尼、派姆单抗+阿西替尼、avelumab+阿西替尼、派姆单抗+乐伐替尼已获批用于晚期肾细胞癌（RCC），派姆单抗+乐伐替尼用于子宫内膜癌，卡瑞利珠单抗+利沃塞尼布用于肝细胞癌。肝细胞癌）。目前，几种 ICI-TKI 组合正在各种其他癌症实体的 I 至 III 期试验中进行研究。此外，ICI-TKI 组合的最佳序列是一个重要的研究课题，因为观察到了物质类别之间的交叉耐药性。该综述报告了 ICI-TKI 组合在不同癌症实体中的临床试验、其疗效和毒性。