Initially unresectable hepatocellular carcinoma treated by combination therapy of tyrosine kinase inhibitor and anti-PD-1 antibody followed by resection.

Abstract

e16690 Background: Combination of tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody showed a high tumor response for advanced hepatocellular carcinoma (HCC). We are aiming to study the effect of combination therapy followed by resection in pts with initially unresectable HCC. Methods: 60 consecutive pts with unresectable or advanced HCC were treated with combination therapy as first-line treatment, including 2 in BCLC-A (China Liver Cancer stage [CNLC]-Ib), and 13 in BCLC-B (CNLC-IIa and IIb), 26 in BCLC-C (vascular invasion, CNLC-IIIa) and 19 in BCLC-C (extrahepatic metastasis, CNLC-IIIb). Tumor response and resectability were evaluated by imaging every 2 months (± 1 week). The criteria of resectability included: (1) R0 resection can be achieved; (2) remnant liver volume ≥ 40%; (3) Child-Pugh score is 5; (4) no contra-indications for hepatectomy. Results: Conversion to resectable HCC was identified in 11 (18.3%) pts after combination therapy. Of them, 2 pts are still under treatment for immune-related adverse events, and 9 underwent hepatectomy as of January 2020. Of the 9 pts, the initial tumor was unresectable because of macro-vascular invasion (n = 6, 1 Vp3, 3 Vp4, 1 hepatic vein, 1 inferior vena cava), extrahepatic metastasis (n = 1, right adrenal gland), tumor nodules ≥ 4 (n = 1) and recurrent HCC within 2 months after first resection (n = 1). The TKIs used were lenvatinib (n = 6) and apatinib (n = 3); anti-PD-1 antibodies used were pembrolizumab (n = 4), sintilimab (n = 3), camrelizumab (n = 1) and nivolumab (n = 1). The median interval between start of combination therapy and resection was 99 days (range, 73–251). The median post-operative hospital stay was 14 days (range, 11–68). The prevalence of post-hepatectomy liver dysfunction (the criteria by ISGLS) is 5 (55.6%) pts, and the post-operative complications (by Clavien–Dindo classification) occurred in 4 (44.4%) pts, including grade I in 1, grade IIIa in 2, and grade V in 1 (died from immune-related adverse events). Tumor response (RECIST v1.1) evaluated before surgery were PR (n = 5), SD (n = 3), and PD (n = 1). Pathological CR (pCR) was found in 5 (55.6%) cases. After a median follow up of 72 days (range, 11–184), tumor recurrence were diagnosed in 1 patient, and mortality without tumor recurrence in 1 patient, the other 7 cases remained tumor-free. Conclusions: This is to date the largest cohort of pts underwent R0 resection after combination therapy for initially un-resectable HCC. The combination of a TKI and anti-PD-1 antibody is feasible as a conversion therapy.