Hepatectomy After Conversion Therapy Using Tyrosine Kinase Inhibitors Plus Anti-PD-1 Antibody Therapy for Patients with Unresectable Hepatocellular Carcinoma

Abstract

Background: Combined treatment with tyrosine kinase inhibitors (TKI) plus anti-PD-1 antibodies showed high anti-tumor efficacy and made conversion resection possible for patients with unresectable hepatocellular carcinoma (HCC). However, long-term survival has not been reported.

Methods: A cohort of consecutive patients who received combined TKI/anti-PD-1 antibodies as first-line treatment for initially unresectable HCC at the authors' hospital between August 2018 and September 2020 was eligible for this study. Patients who were responding to systemic therapy and met the criteria for hepatectomy underwent liver resection with curative intention. The study also investigated the association of clinical factors with successful conversion resection and postoperative recurrence.

Results: The study enrolled 101 patients including 24 patients (23.8 %) who underwent R0 resection a median of 3.9 months (interquartile range: 2.5-5.9 months) after initiation of systemic therapy. Patients with an Eastern cooperative oncology group performance status of 0, fewer intrahepatic tumors, or a radiographic response to systemic therapy were more likely to be able to receive curative resection. After a median follow-up period of 21.5 months, hepatectomy was independently associated with a favorable overall survival (hazard ratio [HR], 0.050; 95 % confidence interval [CI], 0.007-0.365; P = 0.003). For the 24 patients who underwent surgery, the 12-month recurrence-free survival and overall survival rates were respectively 75% and 95.8%. Achieving a pathologic complete response (n = 10) to systemic therapy was associated with a favorable recurrence-free survival after resection, with a trend toward significance (HR, 0.345; 95% CI, 0.067-1.785; P = 0.187).

Conclusions: Selected patients with initially unresectable HCC can undergo hepatectomy after systemic therapy with combined TKI/anti-PD-1 antibodies. In this study, conversion resection was associated with a favorable prognosis.

Conflict of interest statement

Hui-Chuan Sun Sun has received speaker fees from Bayer, BeiGene, Eisai, Hengrui, Innovent, MSD, Roche, and TopAlliance. Xiao-Dong Zhu has received speaker fees from BeiGene, Eisai, MSD, and Roche. The remaining authors have no conflicts of interest.

© 2022. The Author(s).

Figures

Fig. 1

Cumulative survival plots after systemic therapy initiation for a all patients (n = 101) and b patients who underwent (n = 24) or did not undergo (n = 77) conversion surgery.

Fig. 2

Swimmer plots of the 24 patients who underwent conversion resection. EHS, extrahepatic spread; MVI, macrovascular invasion; R0, R0 resection

Fig. 3

a Cumulative plot of recurrence-free survival for patients who underwent conversion resection. b Patients with a pathologic complete response (pCR) had a trend toward a favorable recurrence-free survival versus those without pCR. c The BCLC stages at baseline were not associated with recurrence-free survival.