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


Authors: McKay, R. R.; Bosse, D.; Xie, W.; Wankowicz, S. A. M.; Flaifel, A.; Brandao, R.; Lalani, A. K. A.; Martini, D. J.; Wei, X. X.; Braun, D. A.; Van Allen, E.; Castellano, D.; De Velasco, G.; Wells, J. C.; Heng, D. Y.; Fay, A. P.; Schutz, F. A.; Hsu, J.; Pal, S. K.; Lee, J. L.; Hsieh, J. J.; Harshman, L. C.; Signoretti, S.; Motzer, R. J.; Feldman, D.; Choueiri, T. K.
Article Title: The clinical activity of PD-1/PD-L1 inhibitors in metastatic non–clear cell renal cell carcinoma
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. © 2018 American Association for Cancer Research.
Journal Title: Cancer Immunology Research
Volume: 6
Issue: 7
ISSN: 2326-6066
Publisher: American Association for Cancer Research  
Date Published: 2018-07-01
Start Page: 758
End Page: 765
Language: English
DOI: 10.1158/2326-6066.cir-17-0475
PROVIDER: scopus
PUBMED: 29748390
DOI/URL:
Notes: Article -- Export Date: 4 September 2018 -- Source: Scopus
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MSK Authors
  1. Robert Motzer
    707 Motzer
  2. Darren Richard Feldman
    164 Feldman