Neoadjuvant cabozantinib and nivolumab convert locally advanced hepatocellular carcinoma into resectable disease with enhanced antitumor immunity
Mené sur 15 patients atteints d'un carcinome hépatocellulaire de stade localement avancé, cet essai de phase IB évalue la faisabilité et l'intérêt, du point du vue de la qualité des marges de résection et de la réponse pathologique, d'un traitement adjuvant combinant cabozantinib et nivolumab
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.