Article
Author: Dekervel, Jeroen ; Ji, Fanpu ; Finkelmeier, Fabian ; Piseddu, Ignazio ; Venerito, Marino ; Gorgulho, Joao ; Peck-Radosavljevic, Markus ; Ben Khaled, Najib ; Trauner, Michael ; Parikh, Neehar D. ; Saborowski, Anna ; Reiter, Florian P. ; Vivaldi, Caterina ; Kudo, Masatoshi ; Krall, Anja ; Schwacha-Eipper, Birgit ; Vogel, Arndt ; Balcar, Lorenz ; Wang, Hung-Wei ; Gao, Xu ; Pinter, Matthias ; Cheng, Long ; Masi, Gianluca ; Philipp, Alexander ; Dufour, Jean-François ; von Felden, Johann ; Adžić, Gordan ; Sinner, Friedrich ; Huang, Yi-Hsiang ; Saeed, Anwaar ; Scheiner, Bernhard ; Pinato, David J. ; Stauber, Rudolf ; Schultheiss, Michael ; Lampichler, Katharina ; Bouattour, Mohamed ; Peeters, Frederik ; Geier, Andreas ; Chon, Hong Jae ; Zarka, Valentina ; Bengsch, Bertram ; Nishida, Naoshi ; Hucke, Florian ; Bathon, Melanie ; Yuan, Xiao ; Prejac, Juraj ; Djanani, Angela ; Tesini, Giulia ; Guo, Jiang ; Kang, Beodeul ; Pomej, Katharina ; Weinmann, Arndt ; Lee, Pei-Chang ; Himmelsbach, Vera ; Schulze, Kornelius ; Rimassa, Lorenza ; D’Alessio, Antonio ; Radu, Iuliana-Pompilia
Background and Aims::The outcome of patients with HCC who achieved complete response (CR) to immune-checkpoint inhibitor (ICI)–based systemic therapies is unclear.
Approach and Results::Retrospective study of patients with HCC who had CR according to modified Response Evaluation Criteria in Solid Tumors (CR-mRECIST) to ICI-based systemic therapies from 28 centers in Asia, Europe, and the United States. Of 3933 patients with HCC treated with ICI-based noncurative systemic therapies, 174 (4.4%) achieved CR-mRECIST, and 97 (2.5%) had CR according to RECISTv1.1 (CR-RECISTv1.1) as well. The mean age of the total cohort (male, 85%; Barcelona-Clinic Liver Cancer-C, 70%) was 65.9±9.8 years. The majority (83%) received ICI-based combination therapies. Median follow-up was 32.2 (95% CI: 29.9–34.4) months. One- and 3-year overall survival rates were 98% and 86%. One- and 3-year recurrence-free survival rates were excellent in patients with CR-mRECIST-only and CR-RECISTv1.1 (78% and 55%; 70% and 42%). Among patients who discontinued ICIs for reasons other than recurrence, those who received immunotherapy for ≥6 months after the first mRECIST CR had a longer recurrence-free survival than those who discontinued immunotherapy earlier (p=0.008). Of 9 patients who underwent curative surgical conversion therapy, 8 (89%) had pathological CR (CR-RECISTv1.1, n= 2/2; CR-mRECIST-only, n= 6/7).
Conclusions::Overall survival and recurrence-free survival of patients with CR-mRECIST-only and CR-RECISTv1.1 were excellent, and 6 of 7 patients with CR-mRECIST-only who underwent surgical conversion therapy had pathological CR. Despite potential limitations, these findings support the use of mRECIST in the context of immunotherapy for clinical decision-making. When considering ICI discontinuation, treatment for at least 6 months beyond CR seems advisable.