Immune-related pathologic response (irPR) features and immunotherapeuticresponse score (ITRS) to predict survival following neoadjuvant combined immunotherapy in hepatocellular carcinoma.

Abstract

e16312 Background: A prospective, single-arm, open-label exploratory, phase II study (ChiCTR2000035901) aims to explore the safety and efficacy of Sintilimab plus Anlotinib in unresectable ICC. Methods: Eligible unresectable ICC patients received Sintilimab (200 mg, iv, d1) and Anlotinib (12 mg, po, d1-14) every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was the overall response rate (ORR) assessed by RECIST v1.1 and secondary endpoints included progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), overall survival (OS), surgical conversion rate, as well as safety and tolerability. Results: By the end of Dec. 2024, 28 patients were enrolled with a median age of 60.3 years (range 36-74), 57.1% were male, and all patients were classified as Child-Pugh A. 26 of 28 patients (92.9%) presented with TNM stage IIIb/IV and 11 (11/28, 39.3%) patients had distant metastasis. Confirmed ORR was 42.9% and DCR was 85.7%. Of these, 7.1% (2/28) patients achieved complete response (CR), and 35.7% (10/28) patients achieved partial response (PR). Median PFS was 8.70 months (95% CI: 4.01-13.39) and median OS was 18.33 (95% CI: 11.71-24.95). Among those, 7 (25.0%) patients further received surgical resection, and 3 of them remained disease-free survival at the last follow-up. Treatment-related AEs (TRAEs) occurred in 23/28 pts (82.1%), with the most common being hypertension in 57.1%. Grade 3 TRAEs occurred in 9/28 pts (32.1%), and there was no grade 4-5 TRAEs. Conclusions: Given its encouraging efficacy and safety profile, Sintilimab plus Anlotinib might represent a viable and safe chemotherapy-free regimen in unresectable ICC treatment. Baseline characteristics of patients. Clinical and pathologic indexes Responders 　 Non-Responders P (CR+PR) (n=12) (SD+PD) (n=16) N % 　 N % Age(years) ≤50 3 25.00% 2 12.50% 0.624 >50 9 75.00% 14 87.50% Gender Female 7 58.30% 5 31.25% 0.250 Male 5 41.70% 11 68.75% ALT, U/L ≤50 10 83.30% 13 81.25% 1.000 >50 2 16.67% 3 18.75% GGT, U/L ≤60 2 16.67% 2 12.50% 1.000 >60 10 83.30% 14 87.50% Albumin, g/L <35 12 100.00% 14 87.50% 0.492 ≥35 0 0.00% 2 12.50% PT, s ≤13 12 100.00% 13 81.25% 0.238 >13 0 0.00% 3 18.75% HBsAg Negative 11 91.67% 14 87.50% 1.000 Positive 1 8.33% 2 12.50% CA19-9, U/mL ≤34 3 25.00% 2 12.50% 0.624 >34 9 75.00% 14 87.50% Maximal primary tumor diameter, cm ≤5 2 16.67% 1 6.25% 0.560 >5 10 83.30% 15 93.25% Intrahepatic tumor number Single 8 66.67% 10 62.50% 1.000 Multiple 4 33.33% 6 37.50% Lymph gland metastasis No 3 25.00% 2 12.50% 0.624 Yes 9 75.00% 14 87.50% Distance metastasis No 10 83.30% 7 43.75% 0.054 Yes 2 16.67% 9 56.25% Abbreviation: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; HBsAg, hepatitis B surface antigen; ALT, alanine aminotransferase; GGT, γ-glutamyl transpeptidase; PT, prothrombin time.