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 language | English (US) |
|---|---|
| Pages (from-to) | 749-757 |
| Number of pages | 9 |
| Journal | Nature Medicine |
| Volume | 24 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2018 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. / McDermott, David F.; Huseni, Mahrukh A.; Atkins, Michael B.; Motzer, Robert J.; 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.
In: Nature Medicine, Vol. 24, No. 6, 01.06.2018, p. 749-757.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma
AU - McDermott, David F.
AU - Huseni, Mahrukh A.
AU - Atkins, Michael B.
AU - Motzer, Robert J.
AU - Rini, Brian I.
AU - Escudier, Bernard
AU - Fong, Lawrence
AU - Joseph, Richard W
AU - Pal, Sumanta K.
AU - Reeves, James A.
AU - Sznol, Mario
AU - Hainsworth, John
AU - Rathmell, W. Kimryn
AU - Stadler, Walter M.
AU - Hutson, Thomas
AU - Gore, Martin E.
AU - Ravaud, Alain
AU - Bracarda, Sergio
AU - Suárez, Cristina
AU - Danielli, Riccardo
AU - Gruenwald, Viktor
AU - Choueiri, Toni K.
AU - Nickles, Dorothee
AU - Jhunjhunwala, Suchit
AU - Piault-Louis, Elisabeth
AU - Thobhani, Alpa
AU - Qiu, Jiaheng
AU - Chen, Daniel S.
AU - Hegde, Priti S.
AU - Schiff, Christina
AU - Fine, Gregg D.
AU - Powles, Thomas
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85048001150&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048001150&partnerID=8YFLogxK
U2 - 10.1038/s41591-018-0053-3
DO - 10.1038/s41591-018-0053-3
M3 - Article
C2 - 29867230
AN - SCOPUS:85048001150
VL - 24
SP - 749
EP - 757
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 6
ER -