@article{8f277ee1651f4074a442a28cf30ad893,
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.",
author = "McDermott, {David F.} and Huseni, {Mahrukh A.} and Atkins, {Michael B.} and Motzer, {Robert J.} and Rini, {Brian I.} and Bernard Escudier and Lawrence Fong and Joseph, {Richard W.} and Pal, {Sumanta K.} and Reeves, {James A.} and Mario Sznol and John Hainsworth and Rathmell, {W. Kimryn} and Stadler, {Walter M.} and Thomas Hutson and Gore, {Martin E.} and Alain Ravaud and Sergio Bracarda and Cristina Su{\'a}rez and Riccardo Danielli and Viktor Gruenwald and Choueiri, {Toni K.} and Dorothee Nickles and Suchit Jhunjhunwala and Elisabeth Piault-Louis and Alpa Thobhani and Jiaheng Qiu and Chen, {Daniel S.} and Hegde, {Priti S.} and Christina Schiff and Fine, {Gregg D.} and Thomas Powles",
note = "Funding Information: The authors thank A. Bailey for her contributions to development of the protocol and Z. Boyd for his contributions to the development of the PD-L1 IHC assay and its implementation in this study. Support for third-party writing assistance for this manuscript—by P.S. Davies of Health Interactions, Inc.—was provided by F. Hoffmann-La Roche, AG. This study was sponsored by F. Hoffmann-La Roche, AG. Authors were funded by NCI grants P50 CA101942-13 to D.F.M, M.B.A., and T.K.C.; P30 CA008748 to R.J.M.; and P30 CA14599 to W.M.S. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = jun,
day = "1",
doi = "10.1038/s41591-018-0053-3",
language = "English (US)",
volume = "24",
pages = "749--757",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "6",
}