Outcomes of Post-Immunotherapy Durable Responders of Advanced Hepatocellular Carcinoma- with Emphasis on Locoregional Therapy for Oligoprogression

Abstract

Introduction: The progression patterns, dispositions, and outcomes of patients with advanced hepatocellular carcinoma (HCC) who achieved durable responses with immunotherapy remain poorly characterized.

Methods: Patients with advanced HCC who received immune checkpoint inhibitor (ICI)-based immunotherapy and achieved durable responses were retrospectively included. A durable response was defined as partial response (PR) or stable disease (SD) per RECIST 1.1 for more than 8 months after initiation of immunotherapy. Oligoprogression and polyprogression were defined as progression at ≤3 and >3 lesions, respectively.

Results: A total of 91 durable responders (63 PR and 28 SD) were identified. The majority had chronic viral hepatitis (n = 69, 75.8%). Forty-seven (51.6%) and 44 (48.4%) patients received the index immunotherapy as first-line and second- or beyond-line therapy, respectively. Fifty-four (59.3%) patients subsequently developed progression, with a predominant pattern of oligoprogression (66.7%). The median overall survival (OS) was 46.2 months (95% CI: 34.1-58.3). For patients with subsequent progression, employment of locoregional therapy (LRT) for progression was associated with prolonged OS (univariate analysis: hazard ratio [HR] 0.397, p = 0.009; multivariate analysis: HR 0.363, p = 0.050). Patients with oligoprogression who received LRT showed longer median OS than those who did not (48.4 vs. 20.5 months, p < 0.001). In contrast, the median OS of patients with polyprogression who received LRT was not different from those without LRT (27.7 vs. 25.5 months, p = 0.794).

Conclusion: Approximately 60% of the post-immunotherapy durable responders of HCC subsequently develop progression. Proactive LRT may further rescue patients who develop subsequent oligoprogression. Prospective studies are mandatory to clarify the proper management of durable responders with subsequent progression.

Keywords: Durable response; Hepatocellular carcinoma; Immunotherapy; Locoregional therapy; Oligoprogression.

Fig. 1.

Patient flowchart. The patient flowchart summarizes the progression patterns and LRT utilization in the entire cohort of durable responders.

Fig. 2.

OS of all durable responders. a Kaplan-Meier OS curve of the entire cohort of patients who exhibited a durable response. b Kaplan-Meier OS curves depicting a comparison between 2 subgroups: patients who experienced ongoing durable responses and those who subsequently developed progression. OS, overall survival; CI, confidence interval. ^a There were 8 deaths noted in the ongoing durable response group. Six patients died of infection/pneumonia, and 1 each died of severe gastrointestinal bleeding and complications of cirrhosis.

Fig. 3.

OS of durable responders who subsequently developed progression. a Kaplan-Meier overall survival curves depicting a comparison between 2 subgroups: patients with subsequent progression who received locoregional therapy (LRT) and the corresponding subgroup who did not receive LRT. b Left panel: Kaplan-Meier OS curves depicting a comparison between 2 subgroups: patients who developed subsequent oligoprogression and received LRT, and the corresponding subgroup who did not receive LRT; right panel: Kaplan-Meier OS curves illustrating a comparison between 2 subgroups: patients who subsequently developed polyprogression and received LRT and the corresponding subgroup who did not receive LRT. OS, overall survival; CI, confidence interval.