Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC

Rohini Sharma, Anjana Pillai, Thomas Urban Marron, Petros Fessas, Anwaar Saeed, Tomi Jun, Sirish Dharmapuri, David Szafron, Abdul Rafeh Naqash, Anuhya Gampa, Yinghong Wang, Uqba Khan, Mahvish Muzaffar, Chieh Ju Lee, Pei Chang Lee, Anushi Bulumulle, Sonal Paul, Dominic Bettinger, Hannah Hildebrand, Mohammed YehiaTiziana Pressiani, Ahmed Kaseb, Yi Hsiang Huang, Celina Ang, Masatoshi Kudo, Naoshi Nishida, Nicola Personeni, Lorenza Rimassa, David James Pinato

Research output: Contribution to journalArticlepeer-review


The availability of immune checkpoint inhibitors (ICIs) for the management of advanced hepatocellular cancer (HCC) has changed the treatment paradigm. There are emerging questions regarding the efficacy of subsequent anticancer therapies. The primary aim of this retrospective, multicenter study was to examine the types of anticancer treatment received after ICIs and to assess the impact on post-ICI survival. We established an international consortium of 11 tertiary-care referral centers located in the USA (n = 249), Europe (n = 74), and Asia (n = 97), and described patterns of care following ICI therapy. The impact of subsequent therapy on overall survival (OS) was estimated using the Kaplan–Meier method and presented with a 95% confidence interval (CI). A total of 420 patients were treated with ICIs for advanced HCC after one line of systemic therapy (n = 371, 88.8%): 31 (8.8%) had died, 152 (36.2%) received best supportive care (BSC) following ICIs, and 163 patients (38.8%) received subsequent anticancer therapy. Tyrosine kinase inhibitors (TKIs, n = 132, 80.9%), in particular sorafenib (n = 49, 30.0%), were the most common post-ICI therapy followed by external beam radiotherapy (n = 28, 17.2%), further immunotherapy (n = 21, 12.9%), locoregional therapy (n = 23, 14.1%), chemotherapy (n = 9, 5.5%), and surgery (n = 6, 3.6%). Receipt of post-ICI therapy was associated with longer median OS compared with those who had received BSC (12.1 vs. 3.3 months; hazard ratio [HR]: 0.4 (95% CI: 2.7–5.0). No difference in OS was noted in those patients who received TKI before ICIs compared with those who received ICIs followed by TKI. Conclusion: Post-ICI therapy is associated with OS in excess of 12 months, suggesting a role for therapeutic sequencing. OS from TKI therapy was similar to that reported in registration studies, suggesting preserved efficacy following ICIs.

Original languageEnglish
Pages (from-to)1776-1785
Number of pages10
JournalHepatology Communications
Issue number7
StatePublished - Jul 2022


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