Camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and hepatic artery infusion chemotherapy for hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (TRIPLET): a phase II study

Abstract

Hepatic arterial infusion chemotherapy (HAIC) using a combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promise for hepatocellular carcinoma (HCC) patients classified under Barcelona Clinic Liver Cancer (BCLC) stage C. In China, the combined therapy of camrelizumab and apatinib is now an approved first-line approach for inoperable HCC. This study (NCT04191889) evaluated the benefit of combining camrelizumab and apatinib with HAIC-FOLFOX for HCC patients in BCLC stage C. Eligible patients were given a maximum of six cycles of HAIC-FOLFOX, along with camrelizumab and apatinib, until either disease progression or intolerable toxicities emerged. The primary outcome measured was the objective response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Thirty-five patients were enrolled. Based on RECIST v1.1 criteria, the confirmed ORR stood at 77.1% (95% CI: 59.9% to 89.6%), with a disease control rate of 97.1% (95% CI: 85.1% to 99.9%). The median progression-free survival was 10.38 months (95% CI: 7.79 to 12.45). Patient quality of life had a transient deterioration within four cycles of treatment, and generally recovered thereafter. The most frequent grade ≥3 or above treatment-related adverse events included reduced lymphocyte count (37.1%) and diminished neutrophil count (34.3%). The combination of camrelizumab, apatinib, and HAIC demonstrated encouraging results and manageable safety concerns for HCC at BCLC stage C.

Fig. 1

Patient flowchart

Fig. 2

Treatment response and duration. a Best percentage changes from baseline in target lesions per RECIST v1.1; b best percentage changes from baseline in target lesions per mRECIST; c treatment exposure and response duration per RECIST v1.1; and d treatment exposure and response duration per mRECIST

Fig. 3

Survival analysis. a Kaplan–Meier curves of progression-free survival (PFS) per RECIST v1.1; b Kaplan–Meier curves of PFS per mRECIST; c Kaplan–Meier curves of liver-specific PFS per RECIST v1.1; d Kaplan–Meier curves of liver-specific PFS per mRECIST