Complete Response to Immunotherapy in HCC: Insights From IMbrave150

While immunotherapy is the preferred front-line treatment method for patients with hepatocellular carcinoma (HCC), only a small number of patients achieve complete response, which results in a lack of radiographic apparent disease. It is not well known if clinical or molecular features may define HCCs sensitive to immunotherapies.

To determine the long-term survival outcomes and characteristics of patients with advanced HCC who achieve complete response from immunotherapy, a recent post hoc analysis examined patient data from the IMbrave150 trial and a multicenter cohort analysis.

The main outcome was overall survival (OS) based on the time from the start of immunotherapy to the date of death. OS and progression-free survival (PFS) were measured using Kaplan-Meier curves, while log-rank tests were used to measure differences in survival outcomes.

IMbrave150 enrolled 501 patients. The analytical sample included 279 patients treated with atezolizumab and bevacizumab and 194 patients treated with frontline anti-programmed cell death 1 ligand 1 (PD-1/L1) therapies in a multicenter patient cohort.

At 2 years, patients with complete response had high disease-free survival rates in both the IMbrave150 (58.0%; 95% CI, 36.2%-74.7%) and multicenter (87.4%; 95% CI, 58.2%-96.7%) cohorts. The OS rates at 2 years for complete responders were 81.1% (95% CI, 64.4%-90.5%) in the IMbrave150 cohort and 93.3% (95% CI, 61.2%-99.0%) in the multicenter cohort.

Disease recurrence was rare in complete responders who discontinued treatment for reasons other than disease progression at a median of 24 months. Unique genetic alterations were not found in complete responders during molecular profiling, but disease with complete response had higher PD-L1 protein expression in the immune cell compartment and lower circulating tumor DNA levels.

This post hoc analysis has found that complete responders with HCC have prolonged survival and durable disease control even after therapy has been discontinued. Further examination of immune cell PD-L1 protein expressions and circulating tumor DNA as biomarkers is warranted.