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

By D. McDermott, M. Huseni, M. Atkins, R. Motzer, B. Rini, B. Escudier, L. Fong, R. Joseph, S. Pal, J. Reeves and 22 more. Nature Medicine, 2018

1,089 citations recorded by the source corpus.

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. An exploratory randomized controlled clinical trial of renal cell carcinoma identifies molecular patterns distinguishing responders to immune checkpoint blockade alone or combined with angiogenesis inhibitor versus angiogenesis inhibitor alone.

Subfields: Oncology, Pulmonary and Respiratory Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/658a6dc807649bb59cbcd89060a93dfb03706f85

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Citations in the corpus

• Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition (2021, neutral): “, 2018), and renal (n = 44; McDermott et al., 2018) (total across these four cohorts, n = 454).”
• Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. (2019, background): “In addition, angiogenesis, T-effector/interferon (IFN)-γ response and myeloid inflammatory gene expression signatures have been suggested to predict response to vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) and immunotherapy [29].”
• VEGF in Signaling and Disease: Beyond Discovery and Development (2019, result): “Recent clinical studies have further supported the role of VEGF in anti-cancer immunity (McDermott et al., 2018).”
• Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma (2019, methodology): “We did not detect an association of tumor mutational burden or neoantigen load with any of these immune subtypes (Table S7), confirming previous reports that indicate that these features do not correlate with ccRCC prognosis (Matsushita et al., 2016; McDermott et al., 2018).”
• Renal cell carcinoma (2017, background): “In addition, angiogenesis, T-effector/interferon (IFN)-γ response and myeloid inflammatory gene expression signatures have been suggested to predict response to vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) and immunotherapy [29].”
• Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer (2019, background): “Promising results in renal cell carcinoma have been obtained for clinical activity and molecular correlates of response to atezolizumab in combination with bevacizumab (McDermott et al., 2018).”
• Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors (2018, background): “Due to enhanced migration of neoantigen specific T cell and attenuated immune suppression caused by anti-angiogenesis and other treatments, it is difficult to predict alteration of immune microenvironment of PD-L1 patient post combination treatment [38, 39].”