A clinical study has reported that the elevated levels of antidrug antibodies (ADA) were associated with poorer clinical outcomes in advanced hepatocellular carcinoma (HCC) patients treated with atezolizumab plus bevacizumab. These findings were published in the journal JAMA Oncology.
In 2020, the FDA granted approval to atezolizumab (immune checkpoint inhibitor) in combination with bevacizumab (anti-angiogenic) for adults with advanced HCC. However, treatment with atezolizumab could elicit ADA responses against it, resulting in reduced efficacy of the immune checkpoint inhibitor. Korean researchers have investigated the association between atezolizumab ADA and clinical outcomes.
The prospective study included 174 patients (discovery cohort: n=61, validation cohort: n=113) with advanced HCC who had received first line atezolizumab plus bevacizumab. Among the study participants many patients were excluded due to reasons such as inadequate sample, consent withdrawal or follow-up loss. Finally, the discovery and validation cohort included 50 and 82 patients, respectively. The serum ADA levels in the participants were measured before and three weeks (cycle 2 day 1 [C2D1]) after the treatment.
The analysis revealed that 9/50 patients in the discovery cohort and 14/82 patients in the validation cohort exhibited higher levels of ADA at C2D1. Moreover, all these patients with elevated ADA showed a reduced response rate (discovery cohort: 34% vs 11%; validation cohort: 29% vs. 7%), worse progression-free survival (discovery cohort: hazard ratio (HR), 2.84 [95% CI]: 1.31-6.13; p=0.005; validation cohort: HR, 2.52 [95% CI] 1.27-5.01; p=0.006), and overall survival (discovery cohort: HR, 3.30 [95% CI]: 1.43-7.64; p=0.003; validation cohort: HR, 5.81 [95% CI] 2.70-12.50; p=0.001) than those with lower levels of ADA.
The findings of this study clearly demonstrate that elevated levels of antidrug antibodies attenuate the efficacy of atezolizumab treatment and thus result in poorer clinical outcomes in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab.
Kim C, Yang H, Kim I, et al. Association of High Levels of Antidrug Antibodies Against Atezolizumab With Clinical Outcomes and T-Cell Responses in Patients With Hepatocellular Carcinoma. JAMA Oncol 2022; Online ahead of print.