In a retrospective study reported in JAMA Network Open, Lim et al found that complete response to immunotherapy as first-line treatment of advanced hepatocellular carcinoma was associated with good outcomes.
Study Details
The study involved analysis of 228 patients who received atezolizumab and bevacizumab in the IMbrave150 trial and an analysis of a multicenter cohort of 194 patients who received PD-1/L1 inhibitors in the first-line setting.
Key Findings
In the IMbrave150 cohort, complete response was observed in 37 of 228 patients. Among complete responders, median progression-free survival and median overall survival were not reached, with a median follow-up of 24 months. At 24 months, the proportion of patients with no evidence of disease progression was 58.0% (95% confidence interval [CI] = 36.2%–74.7%) among complete responders and 7.3% (95% CI = 3.5%–13.1%) among other patients. At 24 months, 81.1% (95% CI = 64.4%–90.5%) of complete responders and 21.2% (95% CI = 15.6%–27.3%) of other patients remained alive. Analysis adjusting for age, sex, race, α-fetal protein, liver disease cause, and extrahepatic disease confirmed that overall survival was better in complete responders vs other patients (hazard ratio [HR] = 0.22, 95% CI = 0.07–0.70).
In the multicenter cohort, complete response was observed in 17 of 194 patients. Among complete responders, median progression-free survival and median overall survival were not reached, with a median follow-up of 29 months. At 24 months, the proportion of patients with no evidence of disease progression was 87.4% (95% CI = 58.2%–96.7%) among complete responders and 19.4% (95% CI = 11.6%–28.7%) among other patients. At 24 months, 93.3% (95% CI = 61.2%–99.0%) of complete responders and 25.5% (95% CI = 16.2%–35.8%) of other patients remained alive. Adjusted analysis confirmed that overall survival was better in complete responders (HR = 0.06, 95% CI = 0.01–0.44).
Disease recurrence was rare among complete responders who discontinued treatment for reasons other than disease progression after a median duration of treatment of 24 months.
Molecular profiling of complete responders did not reveal unique genetic alterations. However, complete response was associated with higher PD-L1 expression in immune cells but not tumor cells and with lower circulating tumor DNA levels.
The investigators concluded: “In this post hoc trial and multicenter cohort analysis of patients with [hepatocellular carcinoma] treated with immunotherapy, complete responders demonstrated prolonged survival and durable disease control even after discontinuation of therapy. Biological features of complete responders were also distinct, and further evaluation of immune cell PD-L1 protein expression and circulating tumor DNA as potential biomarkers is warranted.”
David Hsiehchen, MD, of the Division of Hematology and Oncology, The University of Texas Southwestern Medical Center, Dallas, is the corresponding author of the JAMA Network Open article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
