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

Overview

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.

authors

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

publication date

  • June 4, 2018

Research

keywords

  • Antibodies, Monoclonal
  • Antineoplastic Combined Chemotherapy Protocols
  • Bevacizumab
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Sunitinib

Identity

PubMed Central ID

  • PMC6721896

Scopus Document Identifier

  • 85048001150

Digital Object Identifier (DOI)

  • 10.1093/annonc/mdx760.002

PubMed ID

  • 29867230

Additional Document Info

volume

  • 24

issue

  • 6