Nevena Damjanov, MD
Hatanaka and colleagues investigated whether the etiology of the underlying liver disease affected the efficacy of atezolizumab and bevacizumab (A/B). They reported the results of a retrospective cohort study of 323 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma and Child-Pugh class A cirrhosis who started A/B between September 2020 and December 2021. Patients with viral infection were defined as those who were either serum anti–hepatitis C antibody (anti-HCV Ab)- or hepatitis B surface antigen (HBs-Ag)-positive, while patients with nonviral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. After propensity matching, no significant difference in response rate ([RR] 20.6% vs 24.6% in viral and nonviral patients), disease control rate (68.3% vs 69.0%), progression-free survival ([PFS] 7.0 months vs 6.2 months), or 12-month overall survival ([OS] 65.5% vs 71.7%) was seen. The authors concluded that the underlying etiology of liver disease in patients with HCC does not affect the response to treatment with A/B.
Scheiner and colleagues evaluated the efficacy of immunotherapy in patients with HCC who had already received immune checkpoint inhibitors (ICI) in a previous line of therapy. The authors reported the results of an international, retrospective multicenter study of 58 patients with HCC who received at least two lines of ICI-based therapies. The first ICI was discontinued due to disease progression in 90%. Nonetheless, the RR to the second ICI was 26% (compared with 22% for the first ICI), with a time-to-progression (TTP) of 5.4 months (95% CI, 3.0-7.7) for the first ICI and 5.2 months (95% CI, 3.3-7.0) for the second ICI. Grade 3/4 treatment-related adverse events were observed in 16% and 17% of patients with the first and second ICI, respectively. Therefore, the authors believe that ICI rechallenge is safe and results in a treatment benefit for a similar proportion of HCC patients, as is seen with the first ICI treatment. They suggest that ICI-based regimens should be studied in prospective trials of patients who progressed on first-line immunotherapy.
Finally, Kim and colleagues reported outcomes of patients who developed anti-drug antibodies (ADA) against atezolizumab while on A/B. In this prospective cohort study, 174 patients with advanced HCC who were treated with first-line A/B were tested for serum ADA levels prior to treatment and at 3 weeks (cycle 2 day 1 [C2D1]). Clinically, patients with progressive disease exhibited higher ADA levels (median 65.2 [0-520.4] ng/mL) at C2D1 than responders (0-117.5 ng/mL). Patients with high ADA levels at C2D1 had a reduced response rate (29%-34% vs 7-11%) and worse PFS and OS. The investigators found that very high ADA levels (≥ 1000 ng/mL) at 3 weeks were consistently associated with poor clinical outcomes due to reduced systemic exposure to atezolizumab and impaired proliferation and activation of peripheral CD8-positive T cells. They suggested future validation and standardization of ADA assays to optimize treatment with atezolizumab in patients with uHCC.