TY - JOUR
T1 - Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma
AU - Scheiner, Bernhard
AU - Roessler, Daniel
AU - Phen, Samuel
AU - Lim, Mir
AU - Pomej, Katharina
AU - Pressiani, Tiziana
AU - Cammarota, Antonella
AU - Fründt, Thorben W.
AU - von Felden, Johann
AU - Schulze, Kornelius
AU - Himmelsbach, Vera
AU - Finkelmeier, Fabian
AU - Deibel, Ansgar
AU - Siebenhüner, Alexander R.
AU - Shmanko, Kateryna
AU - Radu, Pompilia
AU - Schwacha-Eipper, Birgit
AU - Ebert, Matthias P.
AU - Teufel, Andreas
AU - Djanani, Angela
AU - Hucke, Florian
AU - Balcar, Lorenz
AU - Philipp, Alexander B.
AU - Hsiehchen, David
AU - Venerito, Marino
AU - Sinner, Friedrich
AU - Trauner, Michael
AU - D'Alessio, Antonio
AU - Fulgenzi, Claudia A.M.
AU - Pinato, David J.
AU - Peck-Radosavljevic, Markus
AU - Dufour, Jean François
AU - Weinmann, Arndt
AU - Kremer, Andreas E.
AU - Singal, Amit G.
AU - De Toni, Enrico N.
AU - Rimassa, Lorenza
AU - Pinter, Matthias
N1 - Funding Information:
D.J.P. acknowledges the infrastructural support provided by Imperial Experimental Cancer Medicine Centre, Cancer Research UK Imperial Centre, the Imperial College BRC and the Imperial College Healthcare NHS Trust Tissue Bank.
Publisher Copyright:
© 2022 The Author(s)
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - Immune checkpoint blocker
KW - Immunotherapy
KW - Liver cancer
KW - Systemic therapy
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U2 - 10.1016/j.jhepr.2022.100620
DO - 10.1016/j.jhepr.2022.100620
M3 - Article
C2 - 36578451
AN - SCOPUS:85144025336
SN - 2589-5559
VL - 5
JO - JHEP Reports
JF - JHEP Reports
IS - 1
M1 - 100620
ER -