The Clinical Activity of PD-1/PD-L1 Inhibitors in Metastatic Non–Clear Cell Renal Cell Carcinoma Academic Article uri icon

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abstract

  • 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. Cancer Immunol Res; 6(7); 758-65. ©2018 AACR.

authors

  • McKay, Rana R
  • Bossé, Dominick
  • Xie, Wanling
  • Wankowicz, Stephanie AM
  • Flaifel, Abdallah
  • Brandao, Raphael
  • Lalani, Aly-Khan
  • Martini, Dylan J
  • Wei, Xiao X
  • Braun, David A
  • Van Allen, Eliezer
  • Castellano, Daniel
  • De Velasco, Guillermo
  • Wells, J Connor
  • Heng, Daniel Y
  • Fay, Andre P
  • Schutz, Fabio A
  • Hsu, JoAnn
  • Pal, Sumanta K
  • Lee, Jae Lyun
  • Hsieh, James J
  • Harshman, Lauren C
  • Signoretti, Sabina
  • Motzer, Robert J
  • Feldman, Darren
  • Choueiri, Toni K

publication date

  • July 2018

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