Guadalupi Valentina, Cartenì Giacomo, Iacovelli Roberto, Porta Camillo, Pappagallo Giovanni, Ricotta Riccardo, Procopio Giuseppe
Istituto Nazionale dei Tumori IRCCS Milano, Milano, Lombardia 20133, Italy.
Responsible for Research and Development Kerubin Digital Therapeutic, Italy.
Ther Adv Urol. 2021 Jun 18;13:17562872211022870. doi: 10.1177/17562872211022870. eCollection 2021 Jan-Dec.
Currently, conventional treatments for metastatic RCC (mRCC) include immune-based combination regimens and/or targeted therapies, the latter mainly acting on angiogenesis, a key element of the process of tumor growth and spread. Although these agents proved able to improve patients' outcomes, drug resistance and disease progression are still experienced by a substantial number of VEGFR-TKIs-treated mRCC patients. Following the inhibition of the VEGF/VEGFRs axis, two strategies have emerged: either specifically targeting resistance pathways, at the same time continuing to inhibit angiogenesis, or using a completely different approach aimed at re-activating the immune system through the use of inhibitors of specific negative immune checkpoints. These two approaches, practically represented by the use of either cabozantinib or nivolumab, seem to remain a rational therapeutic approach also when first-line immune-based combinations are used. The objective of this study is to design a preferential therapeutic pathway for the second-line treatment of mRCC. The procedure applied in this project was a group discussion, based on the Nominal Group Technique (NGT) method in a meeting session, aimed at defining the therapeutic choice for the second-line treatment of mRCC. The NGT process defined the most relevant parameters that, according to the interviewed panelists, clinicians should consider for the selection of the second-line therapy in the context of advanced renal cell carcinoma of mRCC. The algorithm developed for the treatment selection as a result of this process should thus be considered by clinicians as reference for therapy selection.
The result of this paper was the definition of an algorithm intended to suggest a preferential therapeutic pathway considering both the outputs of the Nominal Group Technique (NGT) process and the actual clinical practice and the experience of selected panelists. During the NGT process and the discussion phase, panelists defined the most important parameters to be included in the algorithm that are important for the treatment definition. Cabozantinib and nivolumab are identified as the most reasonable therapeutic options for patients progressing after first-line treatment and are the medication options included in the algorithm for therapy selection.
目前，转移性肾细胞癌（mRCC）的传统治疗方法包括基于免疫的联合方案和/或靶向治疗，后者主要作用于血管生成，这是肿瘤生长和扩散过程中的关键要素。尽管这些药物已被证明能够改善患者的预后，但仍有相当数量接受VEGFR-TKIs治疗的mRCC患者出现耐药和疾病进展。在抑制VEGF/VEGFRs轴之后，出现了两种策略：要么在继续抑制血管生成的同时特异性靶向耐药途径，要么采用完全不同的方法，即通过使用特定负性免疫检查点抑制剂来重新激活免疫系统。这两种方法，实际上分别以卡博替尼或纳武单抗的使用为代表，当使用一线基于免疫的联合治疗时，似乎仍然是一种合理的治疗方法。本研究的目的是设计一种mRCC二线治疗的优先治疗途径。本项目采用的程序是在一次会议上基于名义组技术（NGT）方法进行小组讨论，旨在确定mRCC二线治疗的治疗选择。NGT过程确定了最相关的参数，根据受访专家小组成员的意见，临床医生在选择mRCC晚期肾细胞癌二线治疗时应考虑这些参数。因此，临床医生应将由此过程得出的用于治疗选择的算法视为治疗选择的参考。
本文的结果是定义了一种算法，该算法旨在考虑名义组技术（NGT）过程的结果以及实际临床实践和选定专家小组成员的经验，提出一种优先治疗途径。在NGT过程和讨论阶段，专家小组成员确定了算法中最重要的参数，这些参数对于治疗定义很重要。卡博替尼和纳武单抗被确定为一线治疗后病情进展患者最合理的治疗选择，并且是治疗选择算法中包含的用药选项。
