Abstract
A successful phase III trial for the combination of atezolizumab and bevacizumab (the IMbrave150 trial) in advanced hepatocellular carcinoma has recently been reported. This is groundbreaking because nivolumab and pembrolizumab, both programmed cell death-1 (PD-1) antibodies, have failed to show efficacy as first- and second-line therapeutics, respectively, in phase III clinical trials. Immunotherapy with a combination of atezolizumab and bevacizumab resulted in better survival than treatment with sorafenib for the first time since sorafenib was approved in 2007. The high efficacy of the combination of PD-1/programmed death ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) antibodies is not only due to their additive effects on tumor growth, but also to their reprogramming of the immunosuppressive microenvironment into an immunostimulatory microenvironment. These results were confirmed in a phase Ib trial that showed significantly longer progression-free survival in the atezolizumab plus bevacizumab group than in patients that received atezolizumab alone. These results demonstrate that immunotherapy with a combination of PD-1/PD-L1 and VEGF inhibitors is effective and may result in a reprogramming of the tumor microenvironment. The results of an ongoing phase III trial of a PD-1 antibody in combination with the VEGF receptor tyrosine kinase inhibitor (TKI) are highly anticipated.
Highlights
At the European Society for Medical Oncology (ESMO) Asia in November 2019, the positive results of the IMbrave150 study, a trial which compared the effects of the combination of atezolizumab and bevacizumab with those of sorafenib [1], drew attention to the possibility of immunotherapy with a combination of programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) inhibitors
Updated results from the 104 unresectable hepatocellular carcinoma patients in Arm A were presented at the annual meeting of the European Society for Medical Oncology (ESMO) in Barcelona, in the fall of
In addition to the trial of atezolizumab and bevacizumab described above, other studies are examining the efficacy of combined PD-1/PD-L1 and VEGF inhibition
Summary
At the European Society for Medical Oncology (ESMO) Asia in November 2019, the positive results of the IMbrave150 study, a trial which compared the effects of the combination of atezolizumab and bevacizumab with those of sorafenib [1], drew attention to the possibility of immunotherapy with a combination of programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) inhibitors. VEGF creates a microenvironment that inhibits the function of T cells in the tumor during the effector phase of the immune response [4]. The combination of VEGF and PD-1/PD-L1 inhibitors promotes antitumor immunity according to the four Rs. First, a reversal of the VEGF-mediated inhibition of dendritic cell maturation results in the effective priming and activation of T cells (Recognition) [9].
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