Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

David F. McDermott, Mahrukh A. Huseni, Michael B. Atkins, Robert J. Motzer, Brian I. Rini, Bernard Escudier, Lawrence Fong, Richard W. Joseph, Sumanta K. Pal, James A. Reeves, Mario Sznol, John Hainsworth, W. Kimryn Rathmell, Walter M. Stadler, Thomas Hutson, Martin E. Gore, Alain Ravaud, Sergio Bracarda, Cristina Suárez, Riccardo DanielliViktor Gruenwald, Toni K. Choueiri, Dorothee Nickles, Suchit Jhunjhunwala, Elisabeth Piault-Louis, Alpa Thobhani, Jiaheng Qiu, Daniel S. Chen, Priti S. Hegde, Christina Schiff, Gregg D. Fine, Thomas Powles

Research output: Contribution to journalArticle

202 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)749-757
Number of pages9
JournalNature Medicine
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    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., ... Powles, T. (2018). Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nature Medicine, 24(6), 749-757. https://doi.org/10.1038/s41591-018-0053-3