Neoadjuvant cabozantinib and nivolumab convert locally advanced hepatocellular carcinoma into resectable disease with enhanced antitumor immunity

Won Jin Ho, Qingfeng Zhu, Jennifer Durham, Aleksandra Popovic, Stephanie Xavier, James Leatherman, Aditya Mohan, Guanglan Mo, Shu Zhang, Nicole Gross, Soren Charmsaz, Dongxia Lin, Derek Quong, Brad Wilt, Ihab R. Kamel, Matthew Weiss, Benjamin Philosophe, Richard Burkhart, William R. Burns, Chris ShubertAslam Ejaz, Jin He, Atul Deshpande, Ludmila Danilova, Genevieve Stein-O’Brien, Elizabeth A. Sugar, Daniel A. Laheru, Robert A. Anders, Elana J. Fertig, Elizabeth M. Jaffee, Mark Yarchoan

Research output: Contribution to journalArticlepeer-review

Abstract

A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC) but most patients are not candidates for resection and most resected HCCs eventually recur. Until recently, neoadjuvant systemic therapy for HCC has been limited by a lack of effective systemic agents. Here, in a single-arm phase 1b study, we evaluated the feasibility of neoadjuvant cabozantinib and nivolumab in patients with HCC, including patients outside of traditional resection criteria (ClinicalTrials.gov ID NCT03299946). Of 15 patients enrolled, 12 (80%) underwent successful margin-negative resection and 5 out of 12 (42%) had major pathological responses. In-depth biospecimen profiling demonstrated an enrichment in effector T cells, as well as tertiary lymphoid structures, CD138+ plasma cells, and a distinct spatial arrangement of B cells in responders compared to nonresponders, indicating an orchestrated B cell contribution to antitumor immunity in HCC.

Original languageEnglish (US)
Pages (from-to)891-903
Number of pages13
JournalNature Cancer
Volume2
Issue number9
DOIs
StatePublished - Sep 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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