The clinical activity of PD-1/PD-L1 inhibitors in metastatic non–clear cell renal cell carcinoma

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

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


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.

Original languageEnglish
Pages (from-to)758-765
Number of pages8
JournalCancer immunology research
Issue number7
StatePublished - Jul 2018


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