Organ Specific Responses to First-line Lenvatinib Plus Anti-PD-1 Antibodies in Patients With Unresectable Hepatocellular Carcinoma: a Retrospective Analysis

Abstract

BackgroundWe evaluated organ-specific response rates (OSRRs) to first-line lenvatinib plus anti-PD-1 antibodies in patients with advanced hepatocellular carcinoma (HCC).MethodsThis retrospective analysis included Chinese patients with unresectable/advanced HCC who received first-line lenvatinib (8 mg/day) plus ≥3 infusions of anti-PD-1 antibodies between October 2018 and May 2020. Tumor and macrovascular tumor thrombi (MVTT) treatment responses were evaluated every 2 months using RECIST v1.1. The overall response rate (ORR)/OSRR was defined as the percentage of patients with a best overall response of complete or partial response (CR or PR).ResultsIn total, 60 patients were included in the analysis; 96.7% had measurable intrahepatic lesions, 55% had MVTT and 26.7% had extrahepatic disease. In all 60 patients, the ORR was 33.3%, median progression-free survival was 7.0 months (95% CI, 1.7-12.3) and median overall survival was not reached. The OSRR for MVTT (54.5%) was higher versus intrahepatic tumors (32.8%), extrahepatic lung metastases (37.5%) and lymph node metastases (33.3%). Among 33 patients with intrahepatic tumors and MVTT, 18 had differential responses in each site, including 13 with a better response in MVTT versus intrahepatic lesions. Among 18 patients whose MVTT achieved a radiographic CR or PR, six underwent surgical resection: 4/6 achieved a pathological CR in MVTT and 2/6 in the intrahepatic tumor.ConclusionsFirst-line lenvatinib plus anti-PD-1 antibodies resulted in better tumor responses in MVTT versus intrahepatic lesions. Complete MVTT necrosis may allow downstaging and subsequent eligibility for surgical resection in a proportion of patients with advanced HCC.

Neoadjuvant targeted immunotherapy followed by surgical resection versus upfront surgery for hepatocellular carcinoma with macrovascular invasion: A multicenter study

“…Preoperative targeted immunotherapy allowed more patients with advanced disease to attempt radical surgical resection, thereby greatly prolonging the OS of advanced HCC [29,30]. Evidence from several cohorts illustrates that the combination of targeted therapy and immune therapy, optionally augmented by additional interventions, has yielded improved ORR of 30.0%-80.6% and increased conversion surgery rates of 10.0%-42.4% in patients with advanced HCC [24,26,[31][32][33]. However, little attention has been paid to the difference in postoperative outcomes between upfront surgery and surgical resection after neoadjuvant targeted immunotherapy.…”

“…Previous studies reported prolonged OS, tumor downgrading, lower risk of postoperative recurrence, and tolerable AEs associated with targeted immunotherapy [23][24][25]. HCC with macrovascular invasion is an advancedstage malignancy that may benefit from targeted immunotherapy and subsequent surgical resection [26], but the comparison between surgery following neoadjuvant targeted immunotherapy and upfront surgery in terms of short-term postoperative complications and long-term prognosis remains unclear. Therefore, this multicentered study aimed to investigate the safety and efficacy of targeted immunotherapy followed by surgical resection for HCC with macrovascular invasion, taking upfront surgery as control.…”