Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma

Scheiner B, Roessler D, Phen S, Lim M, Pomej K, Pressiani T, Cammarota A, Fründt TW, von Felden J, Schulze K, Himmelsbach V, Finkelmeier F, Deibel A, Siebenhüner AR, Shmanko K, Radu P, Schwacha-Eipper B, Ebert MP, Teufel A, Djanani A, Hucke F, Balcar L, Philipp AB, Hsiehchen D, Venerito M, Sinner F, Trauner M, D'Alessio A, Fulgenzi CA, Pinato DJ, Peck-Radosavljevic M, Dufour JF, Weinmann A, Kremer A, Singal AG, De Toni EN, Rimassa L, Pinter M (2023)

Publication Type: Journal article

Publication year: 2023


Book Volume: 5

Article Number: 100620

Journal Issue: 1

DOI: 10.1016/j.jhepr.2022.100620


Background & Aims: We investigated the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with hepatocellular carcinoma (HCC) who received ICI-based therapies in a previous systemic line. Methods: In this international, retrospective multicenter study, patients with HCC who received at least two lines of ICI-based therapies (ICI-1, ICI-2) at 14 institutions were eligible. The main outcomes included best overall response and treatment-related adverse events. Results: Of 994 ICI-treated patients screened, a total of 58 patients (male, n = 41; 71%) with a mean age of 65.0±9.0 years were included. Median systemic treatment lines of ICI-1 and ICI-2 were 1 (range, 1-4) and 3 (range, 2-9), respectively. ICI-based therapies used at ICI-1 and ICI-2 included ICI alone (ICI-1, n = 26, 45%; ICI-2, n = 4, 7%), dual ICI regimens (n = 1, 2%; n = 12, 21%), or ICI combined with targeted therapies/anti-VEGF (n = 31, 53%; n = 42, 72%). Most patients discontinued ICI-1 due to progression (n = 52, 90%). Objective response rate was 22% at ICI-1 and 26% at ICI-2. Responses at ICI-2 were also seen in patients who had progressive disease as best overall response at ICI-1 (n = 11/21; 52%). Median time-to-progression at ICI-1 and ICI-2 was 5.4 (95% CI 3.0-7.7) months and 5.2 (95% CI 3.3-7.0) months, respectively. Treatment-related adverse events of grade 3-4 at ICI-1 and ICI-2 were observed in 9 (16%) and 10 (17%) patients, respectively. Conclusions: ICI rechallenge was safe and resulted in a treatment benefit in a meaningful proportion of patients with HCC. These data provide a rationale for investigating ICI-based regimens in patients who progressed on first-line immunotherapy in prospective trials. Impact and implications: Therapeutic sequencing after first-line immune checkpoint inhibitor (ICI)-based therapy for advanced hepatocellular carcinoma (HCC) remains a challenge as no available second-line treatment options have been studied in immunotherapy-pretreated patients. Particularly, the role of ICI rechallenge in patients with HCC is unclear, as data from prospective trials are lacking. We investigated the efficacy and safety of ICI-based regimens in patients with HCC pretreated with immunotherapy in a retrospective, international, multicenter study. Our data provide the rationale for prospective trials investigating the role of ICI-based regimens in patients who have progressed on first-line immunotherapy.

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Scheiner, B., Roessler, D., Phen, S., Lim, M., Pomej, K., Pressiani, T.,... Pinter, M. (2023). Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma. JHEP Reports, 5(1). https://doi.org/10.1016/j.jhepr.2022.100620


Scheiner, Bernhard, et al. "Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma." JHEP Reports 5.1 (2023).

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