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Lenvatinib Combined with New FP Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma: Clinical Efficacy, Vascular Remodeling, and Implications for Immuno-Oncology–Systemic Combination Therapy
by
Susumu Maruta
1,*, 
Yohei Koshima
1,
Yuji Debari
1,
Chihei Sugihara
1,
Gou Takahata
1,
Ryo Tamura
1,
Tadashi Ohshima
1,
Yuji Ono
1,
Yuho Morita
1,
Tomoki Chiba
1,
Satoru Ishida
1,
Hideto Imai
1,
Keisuke Watanabe
1,
Ryo Chinzei
1,
Masanori Takahashi
1 and
Yoshihiko Ooka
2 1
Department of Gastroenterology, Saitama Red Cross Hospital, 1-5 Shintoshin, Chuo-ku, Saitama 330-8553, Japan
2
Chiba Chuo Clinic, 1-1 Honchiba-cho, Chuo-ku, Chiba 260-0014, Japan
*
Author to whom correspondence should be addressed.
Curr. Oncol. 2026, 33(5), 286; https://doi.org/10.3390/curroncol33050286
Submission received: 11 April 2026
/
Revised: 4 May 2026
/
Accepted: 12 May 2026
/
Published: 13 May 2026
Simple Summary
No established treatment exists for patients with unresectable hepatocellular carcinoma (HCC) who do not respond to or cannot tolerate immune checkpoint inhibitor (ICI)-based therapy. We evaluated lenvatinib combined with New FP hepatic arterial infusion chemotherapy (LEN–New FP)—comprising intra-arterial cisplatin–lipiodol followed by continuous 5-fluorouracil infusion—in 14 patients with aggressive, ICI-refractory or -intolerant unresectable HCC. The combination achieved an objective response rate of 85.7% and a disease control rate of 100%, with a median overall survival of 22.8 months from treatment initiation. Most patients were able to proceed to subsequent therapies, including four who underwent curative-intent surgical or ablative procedures. A previously unreported finding was the narrowing of the proper hepatic artery (PHA) observed on serial angiography in the majority of patients, which appears to reflect the cooperative vascular effects of lenvatinib and intra-arterial chemotherapy and may explain the exceptionally high tumor response rate. Serial angiographic assessment of tumor vascularity using a semi-quantitative scoring system further confirmed regression of tumor-feeding vessels in the majority of patients, providing additional evidence for the vascular mechanism underlying this regimen’s antitumor activity. These findings support LEN–New FP as a promising treatment option for patients with advanced HCC after ICI failure.
Abstract
Background/Objectives: Patients with unresectable hepatocellular carcinoma (uHCC) refractory or intolerant to immune checkpoint inhibitor (ICI)-based regimens represent a growing yet therapeutically underserved population with limited treatment options. We investigated the efficacy, safety, and mechanistic underpinnings of lenvatinib combined with New FP hepatic arterial infusion chemotherapy (LEN–New FP) in this challenging clinical setting. Methods: We retrospectively analyzed 14 consecutive patients with uHCC treated with LEN–New FP between April 2022 and March 2025. Tumor response was assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Proper hepatic artery (PHA) diameter was serially measured on angiography as an exploratory assessment of vascular remodeling, and tumor vascularity was semi-quantitatively evaluated using a 4-point angiographic scoring system (Tumor Vascularity Score [TVS]). Results: The cohort comprised BCLC stage B/C (7/7), mALBI grade 1–2b, and 13 of 14 patients with prior ICI-containing therapy. The objective response rate and disease control rate were 85.7% and 100%, including two complete responses. Median overall survival was 22.8 months from LEN–New FP initiation (median follow-up: 15.1 months) and 36.2 months from first-line initiation; median intrahepatic progression-free survival was 10.4 months. A total of 11 of 14 patients (78.6%) transitioned to subsequent therapies, including four curative-intent conversions. PHA narrowing was observed in 10 of 13 evaluable patients (76.9%), with no clear association with hepatic function deterioration. TVS decreased in 10 of 12 evaluable patients (83.3%), with reduction observed in 90.0% of PR/CR cases. Conclusions: LEN–New FP achieved sustained intrahepatic tumor control and encouraging survival in aggressive uHCC, including ICI-refractory or -intolerant disease. The concordant reduction in PHA diameter and tumor vascularity score provides angiographic evidence of VEGFR inhibition-mediated vascular remodeling, offering mechanistic insight into the synergistic antitumor effects of this regimen and supporting LEN–New FP as a promising multimodal strategy within the evolving landscape of HCC treatment.
