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Nat Med. 2018 Jun;24(6):749-757. doi: 10.1038/s41591-018-0053-3. Epub 2018 Jun 4.

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

Author information

1
Beth Israel Deaconess Medical Center, Boston, MA, USA. dmcdermo@bidmc.harvard.edu.
2
Genentech, Inc., South San Francisco, CA, USA.
3
Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA.
4
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
5
Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
6
Gustave Roussy, Villejuif, France.
7
University of California, San Francisco School of Medicine, San Francisco, CA, USA.
8
Mayo Clinic Hospital - Florida, Jacksonville, FL, USA.
9
City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
10
Florida Cancer Specialists, Fort Myers, FL, USA.
11
Yale School of Medicine, New Haven, CT, USA.
12
Sarah Cannon Research Institute, Nashville, TN, USA.
13
Vanderbilt University Medical Center, Nashville, TN, USA.
14
University of Chicago Medicine, Chicago, IL, USA.
15
Texas Oncology - Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA.
16
Royal Marsden Hospital, London, UK.
17
CHU Hopitaux de Bordeaux - Hôpital Saint-André, Bordeaux, France.
18
Ospedale San Donato, Azienda USL Toscana Sudest, Arezzo, Italy.
19
Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
20
Azienda Ospedaliera Universitaria Senese, Center for Immune-Oncology, Siena, Italy.
21
Medizinische Hochschule, Zentrum Innere Medizin, Abt. Hämatologie u. Onkologie, Hannover, Germany.
22
Dana-Farber Cancer Institute, Boston, MA, USA.
23
Roche Products Ltd, Welwyn Garden City, UK.
24
Barts Cancer Institute and the Royal Free Hospital, Queen Mary University of London, London, UK.

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.

PMID:
29867230
PMCID:
PMC6721896
DOI:
10.1038/s41591-018-0053-3
[Indexed for MEDLINE]
Free PMC Article

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