Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma Journal Article
| Authors: | McDermott, D. F.; Huseni, M. A.; Atkins, M. B.; Motzer, R. J.; Rini, B. I.; Escudier, B.; Fong, L.; Joseph, R. W.; Pal, S. K.; Reeves, J. A.; Sznol, M.; Hainsworth, J.; Rathmell, W. K.; Stadler, W. M.; Hutson, T.; Gore, M. E.; Ravaud, A.; Bracarda, S.; Suárez, C.; Danielli, R.; Gruenwald, V.; Choueiri, T. K.; Nickles, D.; Jhunjhunwala, S.; Piault-Louis, E.; Thobhani, A.; Qiu, J.; Chen, D. S.; Hegde, P. S.; Schiff, C.; Fine, G. D.; Powles, T. |
| Article Title: | Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma |
| Abstract: | We describe results from IMmotion150, a randomized phase 2 study of atezolizumab (anti-PD-L1) alone or combined with bevacizumab (anti-VEGF) versus sunitinib in 305 patients with treatment-naive metastatic renal cell carcinoma. Co-primary endpoints were progression-free survival (PFS) in intent-to-treat and PD-L1+ populations. Intent-to-treat PFS hazard ratios for atezolizumab + bevacizumab or atezolizumab monotherapy versus sunitinib were 1.0 (95% confidence interval (CI), 0.69-1.45) and 1.19 (95% CI, 0.82-1.71), respectively; PD-L1+ PFS hazard ratios were 0.64 (95% CI, 0.38-1.08) and 1.03 (95% CI, 0.63-1.67), respectively. Exploratory biomarker analyses indicated that tumor mutation and neoantigen burden were not associated with PFS. Angiogenesis, T-effector/IFN-γ response, and myeloid inflammatory gene expression signatures were strongly and differentially associated with PFS within and across the treatments. These molecular profiles suggest that prediction of outcomes with anti-VEGF and immunotherapy may be possible and offer mechanistic insights into how blocking VEGF may overcome resistance to immune checkpoint blockade. © 2018 The Author(s). |
| Journal Title: | Nature Medicine |
| Volume: | 24 |
| Issue: | 6 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2018-06-01 |
| Start Page: | 749 |
| End Page: | 757 |
| Language: | English |
| DOI: | 10.1038/s41591-018-0053-3 |
| PROVIDER: | scopus |
| PUBMED: | 29867230 |
| PMCID: | PMC6721896 |
| DOI/URL: | |
| Notes: | Erratum issued, see DOI: 10.1038/s41591-018-0235-z -- Article -- Export Date: 2 July 2018 -- Source: Scopus |
