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 |
| PMCID: | PMC6712567 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 September 2018 -- Source: Scopus |
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