The Outcome of Conversion Liver Resection Surgery by Lenvatinib Treatment: A Single Center Experience

HIDAKA, MASAAKI; Hara, Takanobu; Soyama, Akihiko; Sasaki, Ryu; Matsushima, Hajime; Tanaka, Takayuki; Hamada, Takashi; Imamura, Hajime; Adachi, Tomohiko; Kanetaka, Kengo; Miyaaki, Hisamitsu; Okano, Shinji; EGUCHI, Susumu

doi:10.21873/anticanres.15791

Cited by 9 publications

(4 citation statements)

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“…Previous retrospective studies have reported resection rates of 15.0% [ 22 ], 2.8% [ 23 ], 88.9% [ 24 ], and 21.8% [ 25 ] for advanced HCC after lenvatinib therapy, respectively. The reason for the variability in these resection rates may be due to the different background characteristics of the patients and the varying durations of lenvatinib therapy, which ranged from 8 weeks to 6 months.…”

Section: Discussionmentioning

confidence: 99%

A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial)

Ichida,

Arita,

Hatano

et al. 2023

Liver Cancer

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Introduction: The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods: In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 min as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions: The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC.

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Section: Discussionmentioning

confidence: 99%

A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial)

Ichida,

Arita,

Hatano

et al. 2023

Liver Cancer

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“…In particular, the combination with ICI has been proven to be a feasible treatment strategy for initially converting uHCC to resectable HCC, with a conversion rate of 15.9% and a pCR rate of 60% 43 . Multiple retrospective studies have shown that the ORR ranged from 33.3% to 55.6% and the conversion rate was between 18.8% and 42.4% in patients with advanced uHCC or HCC with macrovascular invasion who received combination therapy with lenvatinib and anti‐PD‐1 antibodies 44–46 . In addition, the long‐term survival of patients who exhibited a positive response to combined TKI/anti‐PD‐1 antibodies and fulfilled the eligibility criteria for conversion resection in initially uHCC has been reported, with 1‐year RFS and OS of 75% and 95.8%, respectively.…”

Section: Targeted and Immunotherapy‐dominated Systemic Therapymentioning

confidence: 99%

“… 43 Multiple retrospective studies have shown that the ORR ranged from 33.3% to 55.6% and the conversion rate was between 18.8% and 42.4% in patients with advanced uHCC or HCC with macrovascular invasion who received combination therapy with lenvatinib and anti‐PD‐1 antibodies. 44 , 45 , 46 In addition, the long‐term survival of patients who exhibited a positive response to combined TKI/anti‐PD‐1 antibodies and fulfilled the eligibility criteria for conversion resection in initially uHCC has been reported, with 1‐year RFS and OS of 75% and 95.8%, respectively. Furthermore, achieving pCR after systemic treatment was strongly correlated with favorable RFS post‐resection.…”

Section: Targeted and Immunotherapy‐dominated Systemic Therapymentioning

confidence: 99%

Conversion therapy for advanced hepatocellular carcinoma in the era of precision medicine: Current status, challenges and opportunities

Wang,

Xu,

Wang

et al. 2024

Cancer Science

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Hepatocellular carcinoma (HCC), the most prevalent malignancy of the digestive tract, is characterized by a high mortality rate and poor prognosis, primarily due to its initial diagnosis at an advanced stage that precludes any surgical intervention. Recent advancements in systemic therapies have significantly improved oncological outcomes for intermediate and advanced‐stage HCC, and the combination of locoregional and systemic therapies further facilitates tumor downstaging and increases the likelihood of surgical resectability for initially unresectable cases following conversion therapies. This shift toward high conversion rates with novel, multimodal treatment approaches has become a principal pathway for prolonged survival in patients with advanced HCC. However, the field of conversion therapy for HCC is marked by controversies, including the selection of potential surgical candidates, formulation of conversion therapy regimens, determination of optimal surgical timing, and application of adjuvant therapy post‐surgery. Addressing these challenges and refining clinical protocols and research in HCC conversion therapy is essential for setting the groundwork for future advancements in treatment strategies and clinical research. This narrative review comprehensively summarizes the current strategies and clinical experiences in conversion therapy for advanced‐stage HCC, emphasizing the unresolved issues and the path forward in the context of precision medicine. This work not only provides a comprehensive overview of the evolving landscape of treatment modalities for conversion therapy but also paves the way for future studies and innovations in this field.

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“…A high-intensity, multimodal antitumor treatment strategy is recommended for the conversion therapy of HCC, and systemic antitumor therapy is one of the primary methods. Some case reports show encouraging conversion resection rates with TKI monotherapy [37][38][39]. Several retrospective and realworld studies have reported that TKIs in combination with immunotherapy as a conversion therapy method for HCC can achieve a conversion resection rate of 10.2-23.8% [40][41][42][43].…”

Section: Conversion Therapy Regimenmentioning

confidence: 99%

Chinese Multidisciplinary Expert Consensus on Immune Checkpoint Inhibitor-Based Combination Therapy for Hepatocellular Carcinoma (2023 Edition)

Liu,

Lu,

Zhou

et al. 2024

Liver Cancer

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Immune checkpoint inhibitor (ICI)-based combination therapy modalities for hepatocellular carcinoma (HCC) have achieved significant efficacy in clinical research and practice and have become the mainstay for the treatment of unresectable HCC. To better help clinicians use combination immunotherapy drugs and regimens rationally, effectively, and safely, the editorial board facilitated a discussion with multidisciplinary experts in the field, adopted the "Delphi" consensus formation method, and finally revised and completed the "Chinese Multidisciplinary Expert Consensus on the Immune Checkpoint Inhibitors (ICIs)-Based Combination Therapy for Hepatocellular Carcinoma (2023 Edition)" on the basis of the 2021 edition. This consensus primarily focuses on the principles and methods of clinical practice of combination therapy based on ICIs, aiming to summarize the recommendations for clinical application based on the latest research and expert experience and provide application guidance for clinicians.

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The Outcome of Conversion Liver Resection Surgery by Lenvatinib Treatment: A Single Center Experience

Cited by 9 publications

References 0 publications

A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial)

A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial)

Conversion therapy for advanced hepatocellular carcinoma in the era of precision medicine: Current status, challenges and opportunities

Chinese Multidisciplinary Expert Consensus on Immune Checkpoint Inhibitor-Based Combination Therapy for Hepatocellular Carcinoma (2023 Edition)

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