Neoadjuvant immunotherapy of hepatocellular carcinoma: A single-institution experience at Mount Sinai.

e16320 Background: Immunotherapy has markedly improved the survival of patients with advanced hepatocellular carcinoma (HCC). Early-stage HCC is potentially curable through surgical resection, though recurrence is seen in up to 70% of patients. Neoadjuvant immunotherapy may reduce the risk of local and distal recurrences and is currently being studied in several early-phase clinical trials. Here we review our single-institution experience of neoadjuvant immunotherapy in 66 patients with resectable HCC. Methods: We identified 17 patients from NCT04123379 (nivolumab alone or in combination with BMS-813160 or BMS-986253), 41 patients from NCT03916627 (cemiplimab alone or cemiplimab plus radiation), and 8 patients who received neoadjuvant nivolumab off protocol. The primary efficacy outcomes include the overall response rate (ORR) as determined by RECIST 1.1, significant tumor necrosis (STN), defined as 70% or more necrosis in resected tumors on pathological examination, and relapse-free survival (RFS). Safety and feasibility were assessed as well; delay of surgery and treatment-related adverse events (TRAE) were tabulated. Data were analyzed using R version 4.4.1. Results: Among 66 patients, 35 patients (53%) received single-agent anti-PD-1 (nivolumab or cemiplimab), 11 patients (17%) received combination immunotherapy, and 20 patients (30%) received radiation with immunotherapy. 52 patients (79%) had viral etiology. 63 (95%) patients received up to 2 doses of pre-operative immunotherapy, and 60 (91%) patients completed surgery as planned, with one patient experiencing delay to surgery due to treatment-related adverse events (defined as surgery more than 4 weeks from the last dose of immunotherapy). 53 out of 60 patients received adjuvant immunotherapy following surgery. 6 patients did not undergo resection for reasons including metastatic diseases (N = 2), inadequate liver remnant (N = 1), progression of disease (N = 2), and severe COPD (N = 1). The ORR by RECIST 1.1 was 15% (N = 10, all partial responses). Of 60 patients who underwent surgery, 10 patients (15%) achieved STN, including 7 patients with complete pathological responses (pCR); 16 patients (24%) had ≥50% tumor necrosis. For patients who underwent resection, the 1-year RFS was 79.2% (95% CI: 69.3% to 90.4%), and the 2-year RFS was 62.7% (95% CI: 50.8% to 77.3%). Three patients experienced serious treatment-related adverse events (TRAEs), including grade 3 hepatitis (N = 1) and pneumonitis (N = 2). Conclusions: Neoadjuvant immunotherapy with anti-PD-1 in patients with resectable HCC appears to be feasible with a generally acceptable safety profile. Further studies are needed to identify optimal immunotherapy regimens to be used in the neoadjuvant setting as well as optimal duration, and larger cohorts are needed to validate the correlation of pathological response with recurrence and survival.