Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy.
Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy.
Int J Mol Sci. 2023 Jan 6;24(2):1096. doi: 10.3390/ijms24021096.
Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous histological group which is 20-25% of those with renal cell carcinoma (RCC). Patients with nccRCC have limited therapeutic options due to their exclusion from phase III randomized trials. The aim of the present study was to investigate the effectiveness and tolerability of pembrolizumabaxitinib combination in chromophobe and papillary metastatic RCC (mRCC) patients enrolled in the I-RARE (Italian Registry on rAre genitor-uRinary nEoplasms) observational ongoing study (Meet-URO 23). Baseline characteristics, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) and toxicities were retrospectively and prospectively collected from nccRCC patients treated in 14 Italian referral centers adhering to the Meet-Uro group, from December 2020 to April 2022. Only patients with chromophobe and papillary histology were considered eligible for the present pre-specified analysis. There were 32 eligible patients who received pembrolizumab-axitinib as first-line treatment, of whom 13 (40%) had chromophobe histology and 19 (60%) were classified as papillary RCC. The DCR was 78.1% whereas ORR was 43.7% (11 patients achieved stable disease and 14 patients obtained partial response: 9/19 papillary, 5/13 chromophobe). Six patients (18.7%) were primary refractory. Median PFS was 10.8 months (95%CI 1.7-11.5). Eleven patients (34.3%) interrupted the full treatment due to immune-related adverse events (irAEs): G3 hepatitis (n = 5), G3 hypophisitis (n = 1), G3 diarrhea (n = 1), G3 pancreatitis (n = 1), G3 asthenia (n = 1). Twelve patients (37.5%) temporarily interrupted axitinib only due to persistent G2 hand-foot syndrome or G2 hypertension. Pembrolizumab-axitinib combination could be an active and feasible first-line treatment option for patients with papillary or chromophobe mRCC.
非透明细胞肾细胞癌（nccRCC）代表了一组异质性的组织学类型，占肾细胞癌（RCC）的 20-25%。由于排除在 III 期随机试验之外，nccRCC 患者的治疗选择有限。本研究的目的是调查 pembrolizumabaxitinib 联合治疗在纳入 I-RARE（意大利罕见的泌尿生殖系肿瘤登记研究）正在进行的观察性研究（Meet-URO 23）的嗜铬细胞瘤和乳头状转移性 RCC（mRCC）患者中的有效性和耐受性。从 2020 年 12 月至 2022 年 4 月，14 家意大利转诊中心的 nccRCC 患者在 Meet-Uro 组的指导下接受了 pembrolizumab-axitinib 作为一线治疗，回顾性和前瞻性地收集了这些患者的基线特征、客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）和毒性。仅对符合本次预设分析的嗜铬细胞瘤和乳头状组织学的患者进行了评估。有 32 名符合条件的患者接受 pembrolizumab-axitinib 作为一线治疗，其中 13 名（40%）为嗜铬细胞瘤，19 名（60%）为乳头状 RCC。DCR 为 78.1%，ORR 为 43.7%（11 名患者为稳定疾病，14 名患者为部分缓解：9/19 名患者为乳头状，5/13 名患者为嗜铬细胞瘤）。6 名患者（18.7%）为原发性耐药。中位 PFS 为 10.8 个月（95%CI 1.7-11.5）。11 名患者（34.3%）因免疫相关不良事件（irAEs）中断了全疗程治疗：G3 肝炎（n=5）、G3 垂体炎（n=1）、G3 腹泻（n=1）、G3 胰腺炎（n=1）、G3 乏力（n=1）。12 名患者（37.5%）因持续的 G2 手足综合征或 G2 高血压仅暂时中断 axitinib 治疗。pembrolizumab-axitinib 联合治疗可能是治疗乳头状或嗜铬细胞瘤 mRCC 患者的一种有效且可行的一线治疗选择。
