Outcomes and prognostic factors in initially unresectable hepatocellular carcinoma treated using conversion therapy with lenvatinib and TACE plus PD-1 inhibitors

Abstract

PurposeTo evaluate the outcomes and prognostic factors for patients using conversion therapy with lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus programmed cell death protein-1 (PD-1) inhibitors (LTP) for initially unresectable hepatocellular carcinoma (iuHCC).MethodsData on 94 consecutive patients with iuHCC who received LTP conversion therapy from November 2019 to September 2022 were retrospectively analyzed. Early tumor response was reported when patients showed complete or partial response at the time of their first follow-up (4–6 weeks) after initial treatment, in accordance with mRECIST. The endpoints consisted of conversion surgery rate, overall survival (OS), and progression-free survival (PFS).ResultsEarly tumor response was found in 68 patients (72.3%) and not in the remaining 26 patients (27.7%) in the entire cohort. Early responders had a significantly higher conversion surgery rate than non-early responders (44.1% vs. 7.7%, p=0.001). Early tumor response was the only factor independently associated with successful conversion resection, as indicated by multivariate analysis (OR=10.296; 95% CI: 2.076–51.063; p=0.004). Survival analysis showed that early responders had longer PFS (15.4 vs. 7.8 months, p=0.005) and OS (23.1 vs. 12.5 months, p=0.004) than non-early responders. Early responders who underwent conversion surgery also had significantly longer median PFS and OS (not reached, not reached) than those who did not (11.2 months, p=0.004; 19.4 months, p<0.001). In multivariate analyses, early tumor response was identified as an independent prognostic factor for longer OS (HR=0.404, 95% CI: 0.171–0.954; p=0.039). Successful conversion surgery was also an independent predictive factor for longer PFS (HR=0.248, 95% CI: 0.099–0.622; p=0.003) and OS (HR=0.147, 95% CI: 0.039–0.554; p=0.005).ConclusionsEarly tumor response is an important predictive marker for successful conversion surgery and prolonged survival in patients with iuHCC treated using LTP conversion therapy. Conversion surgery is necessary to improve survival during conversion therapy, particularly for early responders.

Efficacy and safety of hepatic artery infusion chemotherapy combined with tyrosine kinase inhibitors plus programmed death-1 inhibitors for hepatocellular carcinoma refractory to transarterial chemoembolization

“…Additionally, these HCC patients may be cured only by conversion resection. TACE-based combination therapy is playing an increasingly important role in tumor downstaging and translational surgical resection of unresectable hepatocellular carcinoma because of its better tumor response rate and better survival benefit ( 29 ). Romic et al.…”

“…based combination therapy is playing an increasingly important role in tumor downstaging and translational surgical resection of unresectable hepatocellular carcinoma because of its better tumor response rate and better survival benefit (29). Romic et al reported that this translational surgical resection resulted in better clinical outcomes and a better survival prognosis (30).…”

What Is the Role of Minimally Invasive Liver Surgery in Treating Patients with Hepatocellular Carcinoma on Cirrhosis?

“…Another effective regimen might be TACE followed by hepatic arterial infusion chemotherapy, as reported by Li et al [ 15 ]. Moreover, in patients who successfully underwent conversion therapy, the subsequent surgical treatment appears to be associated with more prolonged survival compared to non-surgical management, albeit with possibly increased perioperative risk [ 16 , 17 , 18 , 19 ]. Finally, the new IMBRAVE trial has shown the effectiveness of adjuvant therapy for the first time in decreasing the risk of post-surgical tumor recurrence in high-risk HCC patients, which was confirmed in widespread reproducibility studies [ 20 , 21 , 22 , 23 , 24 ].…”

Effect of transcatheter arterial chemoembolization combined with lenvatinib plus anti–PD-1 antibodies in patients with unresectable hepatocellular carcinoma: A treatment with Chinese characteristics

“…Although participants' baseline characteristics and the definition of conversion to resectable HCC varied among studies, conversion rates were 25-50%, based on the good ORR performance of triple therapy (16)(17)(18)(19).…”