Feasibility and Efficacy of Neoadjuvant Cabozantinib and Nivolumab in Advanced HCC Patients

For a study, researchers determined that only 10-15% of newly diagnosed hepatocellular carcinoma (HCC) patients meet the criteria for a potentially curative surgical removal, and most patients who undergo resection eventually experience a recurrence. Historical systemic therapies, such as sorafenib and locoregional therapies, have not shown any clinical advantage in the perioperative context. In HCC, innovative amalgamations of targeted therapies and immunotherapies have exhibited superior response rates compared to sorafenib. This report presents the viability and effectiveness of neoadjuvant combination therapy involving cabozantinib and nivolumab, followed by surgical resection, for individuals diagnosed with borderline resectable or locally advanced HCC. Following an open-label, single-arm design, a study was carried out on patients diagnosed with HCC presenting with either borderline resectable or locally advanced HCC. This included cases with multinodular disease, portal vein involvement, or other high-risk features. The patients underwent an 8-week course of therapy consisting of daily oral administration of cabozantinib at a dose of 40 mg and intravenous infusion of nivolumab at 240 mg every two weeks.

Following this treatment, the patients underwent restaging and potential surgical removal of the affected area. The study’s main objective was to assess the feasibility of the treatment. Feasibility was determined by calculating the percentage of patients who encountered a treatment-related adverse event that prevented them from proceeding with surgery within 60 days of the scheduled surgical evaluation. Researchers recruited a total of 15 individuals, out of which 14 completed neoadjuvant therapy and subsequently underwent surgical assessment. Adverse events observed were in line with previous encounters with these therapeutic agents, and the clinical trial successfully achieved its primary objective, as no patients encountered a treatment-associated adverse event that hindered prompt surgical evaluation. Among the patients who underwent neoadjuvant therapy, one patient refused to proceed with the surgical intervention, while another patient’s tumor was deemed unresectable. However, a total of 12 patients successfully underwent R0 surgical resection. Of the patients who underwent resection, 5 out of 12 (41.7%) exhibited a significant or complete pathologic response. At a median follow-up of one year, 80% of pathologic responders remain free from recurrence.

The study represents the initial utilization of a focused, therapeutic approach with an immune checkpoint inhibitor in the neoadjuvant context for HCC. Additionally, it marks the inaugural application of contemporary systemic treatments to broaden the criteria for surgical resection. The feasibility of administering neoadjuvant cabozantinib and nivolumab has been observed, potentially leading to pathologic responses and long-term disease-free survival in a cohort of patients who may fall outside the conventional resection criteria.

Source: https://meetings.asco.org/abstracts-presentations/194333

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03299946

Mark Yarchoan, Qingfeng Zhu, Jennifer N. Durham, Nicole Gross, Soren Charmsaz, James M. Leatherman, Shu Zhang, Aleksandra Popovic, Matthew John Weiss, Benjamin Philosophe, Richard A. Burkhart, William Burns, Brad Wilt, Elizabeth Sugar, Elana J. Fertig, Dan Laheru, Robert A Anders, Elizabeth M. Jaffee, Won Jin Ho/Feasibility and efficacy of neoadjuvant cabozantinib and nivolumab in patients with borderline resectable or locally advanced hepatocellular carcinoma (HCC)./J Clin Oncol 39, 2021 (suppl 3; abstr 335) DOI 10.1200/JCO.2021.39.3_suppl.335.