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

• Published in: JHEP reports Vol. 5; no. 1; p. 100620
• Main Authors: Scheiner, Bernhard, Roessler, Daniel, Phen, Samuel, Lim, Mir, Pomej, Katharina, Pressiani, Tiziana, Cammarota, Antonella, Fründt, Thorben W., von Felden, Johann, Schulze, Kornelius, Himmelsbach, Vera, Finkelmeier, Fabian, Deibel, Ansgar, Siebenhüner, Alexander R., Shmanko, Kateryna, Radu, Pompilia, Schwacha-Eipper, Birgit, Ebert, Matthias P., Teufel, Andreas, Djanani, Angela, Hucke, Florian, Balcar, Lorenz, Philipp, Alexander B., Hsiehchen, David, Venerito, Marino, Sinner, Friedrich, Trauner, Michael, D'Alessio, Antonio, Fulgenzi, Claudia A.M., Pinato, David J., Peck-Radosavljevic, Markus, Dufour, Jean-François, Weinmann, Arndt, Kremer, Andreas E., Singal, Amit G., De Toni, Enrico N., Rimassa, Lorenza, Pinter, Matthias
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2023; Elsevier
• Subjects: Immune checkpoint blocker; Immunotherapy; Liver cancer; Systemic therapy; PR; BOR; OS; HCC; ICI; ORR; CR; Systemic therapy; Liver cancer; SD; TTP; DCR; PD; TRAEs; Immunotherapy; Immune checkpoint blocker; NE; CR, complete response; PR, partial response; ORR, objective response rate; TTP, time-to-progression; BOR, best overall response; DCR, disease control rate; TRAEs, treatment-related adverse events; NE, not evaluable; OS, overall survival; PD, progressive disease; SD, stable disease; ICI, immune checkpoint inhibitor; HCC, hepatocellular carcinoma
• ISSN: 2589-5559; 2589-5559
• DOI: 10.1016/j.jhepr.2022.100620

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. 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. 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. 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. 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. [Display omitted] •ICI rechallenge is uncommon in clinical practice – we screened 994 patients at 14 institutions and identified 58 cases of ICI rechallenge.•ORR, DCR, and median TTP were comparable between first and second ICI-based treatment.•Objective responses were seen in patients with progressive disease as best radiological response during first ICI-based treatment.•They were also observed in those receiving atezolizumab/bevacizumab as a prior ICI regimen.•ICI rechallenge was safe in our cohort and high-grade (grade 3-4) treatment-related adverse events were uncommon.