The Clinical Activity of PD-1/PD-L1 Inhibitors in Metastatic Non-Clear Cell Renal Cell Carcinoma.
The Clinical Activity of PD-1/PD-L1 Inhibitors in Metastatic Non-Clear Cell Renal Cell Carcinoma.
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DOI：
10.1158/2326-6066.cir-17-0475
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发表时间：
2018-07
影响因子：
10.1
通讯作者：
Choueiri TK
中科院分区：
文献类型：
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作者：
McKay RR;Bossé D;Xie W;Wankowicz SAM;Flaifel A;Brandao R;Lalani AA;Martini DJ;Wei XX;Braun DA;Van Allen E;Castellano D;De Velasco G;Wells JC;Heng DY;Fay AP;Schutz FA;Hsu J;Pal SK;Lee JL;Hsieh JJ;Harshman LC;Signoretti S;Motzer RJ;Feldman D;Choueiri TK
程序性死亡1 （PD-1）和PD配体1 （PD- l1）抑制剂在转移性透明细胞肾细胞癌（ccRCC）中显示出活性。这些药物在非透明细胞RCC （nccRCC）或肉瘤样/横纹肌样分化患者中的活性数据有限。在这项多中心分析中，我们探讨了PD-1/PD-L1抑制剂对nccRCC或肉瘤样/横纹肌样分化患者的疗效。收集基线和随访的人口学、临床、治疗和放射学数据。主要终点为客观有效率。次要终点包括治疗失败时间（TTF）、总生存期（OS）和生物标志物相关指标。43例患者包括：乳头状（n = 14, 33%）、恐色（n = 10, 23%）、未分类（n = 9, 21%）、易位（n = 3, 7%）和ccRCC合并肉瘤样分化（n = 7, 16%）。在这43例患者中，11例（26%）患者有肉瘤样和/或横纹肌样分化（7例为ccRCC， 4例为nccRCC）。总体而言，8名患者（19%）客观缓解，包括4名接受PD-1/PD-L1单药治疗的患者（13%）。有肉瘤样和/或横纹肌样分化的ccRCC （n = 3/7, 43%）、易位性RCC （n = 1/3, 33%）和乳头状RCC （n = 4/14, 29%）患者均有应答。中位TTF为4.0个月[95%置信区间（CI）， 2.8-5.5]，中位OS为12.9个月（95% CI， 7.4-未达到）。没有特定的基因组改变与临床获益相关。PD-1/ pd - l1阻滞剂在一些nccRCC患者中观察到适度的抗肿瘤活性。进一步的前瞻性研究需要调查PD-1/ PD-L1阻断在这种异质性患者群体中的疗效。
Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have shown activity in metastatic clear cell renal cell carcinoma (ccRCC). Data on the activity of these agents in patients with non-clear cell RCC (nccRCC) or patients with sarcomatoid/rhabdoid differentiation are limited. In this multicenter analysis, we explored the efficacy of PD-1/PD-L1 inhibitors in patients with nccRCC or sarcomatoid/rhabdoid differentiation. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate. Secondary endpoints include time-to-treatment failure (TTF), overall survival (OS), and biomarker correlates. Forty-three patients were included: papillary (n = 14; 33%), chromophobe (n = 10; 23%), unclassified (n = 9; 21%), translocation (n = 3; 7%), and ccRCC with sarcomatoid differentiation (n = 7, 16%). Of those 43 patients, 11 patients (26%) had sarcomatoid and/or rhabdoid differentiation (n = 7 with ccRCC; n = 4 nccRCC). Overall, 8 patients (19%) objectively responded, including 4 patients (13%) who received PD-1/PD-L1 monotherapy. Responses were observed in patients with ccRCC with sarcomatoid and/or rhabdoid differentiation (n = 3/7, 43%), translocation RCC (n = 1/3, 33%), and papillary RCC (n = 4/14, 29%). The median TTF was 4.0 months [95% confidence interval (CI), 2.8–5.5] and median OS was 12.9 months (95% CI, 7.4-not reached). No specific genomic alteration was associated with clinical benefit. Modest antitumor activity for PD-1/PD-L1-blocking agents was observed in some patients with nccRCC. Further prospective studies are warranted to investigate the efficacy of PD-1/ PD-L1 blockade in this heterogeneous patient population.