Abstract：
OBJECTIVE: The treatment landscape in metastatic renal cell carcinoma (mRCC) has evolved dramatically in recent years. Within the German guideline committee for RCC we evaluated current medical treatments and gave recommendations.
METHODS: A systematic review of published evidence for medical treatment of mRCC was performed (July 2016-August 2019) to cover the duration from last guideline update in 2016. Evidence was graded according to SIGN ( http://www.sign.ac.uk/pdf/sign50.pdf ). Recommendations were made on the basis of a nominal group work with consensus approach and included patient advocates and shareholder of the German RCC treatment landscape. Each recommendation was graded according to its strength as strong recommendation (A) or recommendation (B). Expert statements were given, where appropriate.
RESULTS: Strong first-line recommendations (IA) exist for axitinib + pembrolizumab (all risk categories) and ipilimumab + nivolumab (intermediate or poor risk only). Axitinib + avelumab is a recommended first-line treatment across patients with any risk category (IB). In patients who are not candidates for immune check point inhibitor (ICI) combinations, targeted agents should be offered as an alternative treatment. Subsequent treatment after ICI-based combinations remain ill-defined and no standard of care can be formulated.
CONCLUSIONS: ICI-based combinations are the first-line standard of care and should be considered accordingly. There is an unmet medical need for pivotal studies that define novel standards in patients with failure of ICI-based combinations.
METHODS: A systematic review of published evidence for medical treatment of mRCC was performed (July 2016-August 2019) to cover the duration from last guideline update in 2016. Evidence was graded according to SIGN ( http://www.sign.ac.uk/pdf/sign50.pdf ). Recommendations were made on the basis of a nominal group work with consensus approach and included patient advocates and shareholder of the German RCC treatment landscape. Each recommendation was graded according to its strength as strong recommendation (A) or recommendation (B). Expert statements were given, where appropriate.
RESULTS: Strong first-line recommendations (IA) exist for axitinib + pembrolizumab (all risk categories) and ipilimumab + nivolumab (intermediate or poor risk only). Axitinib + avelumab is a recommended first-line treatment across patients with any risk category (IB). In patients who are not candidates for immune check point inhibitor (ICI) combinations, targeted agents should be offered as an alternative treatment. Subsequent treatment after ICI-based combinations remain ill-defined and no standard of care can be formulated.
CONCLUSIONS: ICI-based combinations are the first-line standard of care and should be considered accordingly. There is an unmet medical need for pivotal studies that define novel standards in patients with failure of ICI-based combinations.
摘要：
目的：近年来，转移性肾细胞癌（mRCC）的治疗前景得到了巨大的发展。在德国RCC指导委员会中，我们评估了当前的药物治疗并给出了建议。
方法：对已发表的mRCC药物治疗证据进行了系统评价（2016年7月至2019年8月），以涵盖2016年上次指南更新的持续时间。根据SIGN（http：//www。sign.AC.uk/pdf/sign50.pdf)。建议是在名义小组工作的基础上提出的，采用共识方法，包括患者倡导者和德国RCC治疗方案的股东。每个建议根据其强度分级为强力建议(A)或建议(B)。专家发言，在适当的地方。
结果：对于阿西替尼+派博利珠单抗（所有风险类别）和伊匹单抗+纳武单抗（仅中等或低风险），存在强有力的一线建议（IA）。阿西替尼+阿维鲁单抗是任何风险类别（IB）患者的推荐一线治疗。在不是免疫检查点抑制剂（ICI）组合候选人的患者中，应提供靶向药物作为替代治疗。基于ICI的组合后的后续治疗仍不明确，无法制定护理标准。
结论：基于ICI的组合是一线护理标准，应相应考虑。对于定义基于ICI的组合失败的患者的新标准的关键研究存在未满足的医学需求。
方法：对已发表的mRCC药物治疗证据进行了系统评价（2016年7月至2019年8月），以涵盖2016年上次指南更新的持续时间。根据SIGN（http：//www。sign.AC.uk/pdf/sign50.pdf)。建议是在名义小组工作的基础上提出的，采用共识方法，包括患者倡导者和德国RCC治疗方案的股东。每个建议根据其强度分级为强力建议(A)或建议(B)。专家发言，在适当的地方。
结果：对于阿西替尼+派博利珠单抗（所有风险类别）和伊匹单抗+纳武单抗（仅中等或低风险），存在强有力的一线建议（IA）。阿西替尼+阿维鲁单抗是任何风险类别（IB）患者的推荐一线治疗。在不是免疫检查点抑制剂（ICI）组合候选人的患者中，应提供靶向药物作为替代治疗。基于ICI的组合后的后续治疗仍不明确，无法制定护理标准。
结论：基于ICI的组合是一线护理标准，应相应考虑。对于定义基于ICI的组合失败的患者的新标准的关键研究存在未满足的医学需求。
