Focus on the frontier, target and lead: "Chinese characteristics" liver cancer must be treated like this!

*Only for medical professionals to read and reference Liver cancer experts will gather at the 2021 CSCO Eisai Levima (Lenvatinib) Satellite Conference to take you into the future of liver cancer treatment! In recent years, in the drug treatment of liver cancer, new treatment models such as targeted drugs and immune drugs have continued to emerge, which have further improved the survival of liver cancer patients
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During the 2021 Chinese Society of Clinical Oncology (CSCO) academic annual meeting held recently, the lenvatinib satellite meeting was held simultaneously.
The meeting invited Professor Qin Shukui from Nanjing Jinling Hospital and Professor Meng Zhiqiang, director of the Minimally Invasive Therapy Center of Fudan University Cancer Hospital, to co-chair the conference.
, The content focuses on the frontier academic progress of liver cancer treatment, shares the real-world clinical diagnosis and treatment data of lenvatinib, explores and interprets the clinical strategy of translational therapy based on the consensus of Chinese experts on the transformation of liver cancer, and at the same time from the new pattern of interventional combined systemic therapy and the combined action mechanism of target immunity In-depth discussion of perspectives
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The chairman of the conference, Professor Qin Shukui, stated in his opening speech that in recent years, targeted drugs for liver cancer have developed rapidly.
Among them, the most significant milestone in the field of liver cancer treatment is lenvatinib.
Its launch is not just a breakthrough in targeted drugs.
It also opens up a broad prospect for the combination of translational therapy, targeting and immunotherapy
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In conversion therapy, lenvatinib is the best with a single-agent objective response rate (ORR) of 43.
8% (mRECIST, Chinese population).
At the same time, in combination immunotherapy, lenvatinib-based systemic therapy Show a great advantage
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It is believed that thanks to the synergistic mechanism of lenvatinib combined with immunotherapy, more lenvatinib combinations will emerge in the future, which will surely bring more breakthroughs and surprises to the field of liver cancer treatment
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Subsequently, Professor Meng Zhiqiang presided over the academic session.
He introduced that with the approval of lenvatinib and its inclusion in the 2020 National Medical Insurance List, it has further boosted the rapid development of comprehensive treatment of liver cancer led by systemic therapy
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This satellite will focus on the latest academic progress of lenvatinib, clinical translational treatment strategies, and in-depth discussions from the introduction of the new pattern of combined systemic therapy and the mechanism of the combined use of targeting and immunization
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The Evidence-Based Pathway of Renvatinib: From RCT to RWS Professor Weidong Wei from the First Affiliated Hospital of University of Science and Technology of China shared a series of studies on Renvatinib from RCT to RWS
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In REFLECT Chinese population data, lenvatinib compared to sorafenib group significantly prolonged overall survival (OS) by 4.
8 months, and progression-free survival (PFS), ORR, and time to disease progression (TTP) were all Sola Nearly 3 times in the fenib group
.

Figure 1.
REFLECT Chinese population data, the lenvatinib group was significantly better than the control group at each end point By week, the ORR can reach more than 50%, and the mode of discontinuing lenvatinib over the weekend is better than reducing the dose
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Professor Weidong Wei concluded that from RCT to RWS, research data comprehensively confirmed the excellent efficacy of lenvatinib in the treatment of uHCC; lenvatinib is not only superior to sorafenib in the first-line treatment of uHCC in ORR and PFS, but also early The response is good, and it is used when the baseline liver function is good, and the patient benefits more
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At the same time, lenvatinib has good safety.
Interrupting the mode of administration on weekends can further improve the tolerability of the treatment, thereby improving the efficacy
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Significance and exploration of transformational therapy for liver cancer In the late stage
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Patients who undergo surgical resection have a better chance of being cured, prolonging their survival period, and improving their quality of life
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Therefore, high ORR and short-term rapid tumor shrinkage are important factors for the success of translational therapy
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Figure 2.
The rapid development of drug therapy has brought transformational opportunities for patients with advanced liver cancer.
The rapid development of targeted therapy, immunotherapy, and targeted immunotherapy has significantly improved the therapeutic effect of liver cancer, prolonged the survival period of advanced patients, and more The transformational therapy of unresectable liver cancer has been realized, bringing more benefits to patients with advanced liver cancer
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The most commonly used combination therapy in clinical practice is lenvatinib combined with PD-1 monoclonal antibody, or other multi-target tyrosine kinase inhibitor (TKI) drugs combined with PD-1 monoclonal antibody
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Professor Sun Huichuan introduced the survival of 23 patients after transformational resection.
As of August 2021, the median follow-up time was 14.
4 months.
The 1-year survival rate was 95.
7% and the 1-year recurrence rate was 25.
1%, including 10 cases.
The patient has stopped anti-tumor therapy and has a good quality of life
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As of December 2020, 23 patients with HCC had undergone transformational resection after TKI+PD-1 monoclonal antibody treatment
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Through case introduction, Professor Sun Huichuan concluded that in clinical practice, patients are more accepting of oral targeted drugs
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Targeted therapy occupies an important position among the approved first-line treatment plans for liver cancer, and the key value of lenvatinib in the treatment of liver cancer cannot be ignored
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Na Zhi Dingxin looks at the new pattern of interventional combined system therapy for liver cancer from the guide update, Professor Ming Zhao from the Cancer Hospital of Sun Yat-sen University shared the new pattern of interventional combined system therapy for liver cancer
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In 2017, a real-world study of 6241 patients in China showed that about 70% of patients are in the middle and advanced stages.
TACE is the main treatment method, and the proportion of patients who prefer TACE treatment accounts for 51%
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Figure 3.
TACE is one of the standard treatments for advanced HCC.
The new version of the "Guidelines for Interventional Therapy of Liver Cancer in China" points out that the basic principle of TACE for liver cancer should be: increase the number of TACE treatments.
If it is not suitable for the original plan, consider combined system therapy
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For liver cancer patients with low tumor burden, TACE therapy alone can get significant clinical benefits.
For patients with moderate tumor burden or high burden that the efficacy of TACE alone is not good, TACE combined with targeted therapy should be started as soon as possible
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The renewal of this concept has become an important trend in combined treatment of liver cancer
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Professor Ming Zhao said that as a new generation of first-line targeted therapy, combined intervention can further optimize the efficacy and bring multiple survival benefits to patients with advanced liver cancer
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The mid-term analysis of the Phase II TACTICS-L study showed that the ORR benefit of lenvatinib combined with TACE was 75.
8%
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A retrospective analysis in China showed that lenvatinib combined with TACE can significantly improve the survival of patients.
Compared with TACE alone, lenvatinib combined with TACE can significantly improve the 1-year and 2-year OS rate and PFS rate of patients.
And ORR
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These studies have verified that lenvatinib is a powerful choice for the "strong combination" of interventional therapy
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Figure 4.
Lenvatinib is a powerful choice for the "strong combination" of interventional therapy.
Lenvatinib dually inhibits the VEGF/FGF pathway, which can effectively prevent recurrence and metastasis
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Animal models have confirmed that lenvatinib can inhibit the development of liver fibrosis and reduce liver damage.
Retrospective studies have shown that more patients in the lenvatinib group maintain or improve liver function than the sorafenib group
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Currently, lenvatinib is the cornerstone of the systemic treatment of liver cancer, and treatment exploration based on lenvatinib combined with various interventional methods is underway, and significant progress has been made
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Professor Ming Zhao said that comprehensive treatment based on lenvatinib can further improve ORR, bring more possibilities for transformation, and expect long-term survival in the future
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Study on the mechanism of targeted combined immunotherapy for hepatocarcinoma combined with longitudinal and horizontal liver cancer.
With the development of molecular biology and molecular immunology, immunotherapy for liver cancer based on immune recognition and effect mechanisms has become one of the current hotspots, and tumor therapy has entered a targeted combination.
The age of immunotherapy
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At the meeting, Professor Liu Xiufeng from Nanjing Jinling Hospital shared the mechanism of targeted combined immunotherapy for liver cancer
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The REFLECT study showed that the PFS and ORR of the lenvatinib group were significantly better than those of the sorafenib group, and it also achieved remarkable results in the field of thyroid cancer treatment
.

The SELECT study confirmed that lenvatinib can significantly improve the ORR and PFS of patients with radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC).
The 308 study confirmed that Chinese RAIR-DTC patients benefited more, with an ORR as high as 69.
9%, with a median of 69.
9%.
PFS is as long as 23.
9 months
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The excellent curative effect of lenvatinib is inseparable from its unique mechanism.
The targets of lenvatinib include VEGFR1-3, FGFR1-4, PDGFRα, RET, and c-KIT
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Through anti-angiogenesis, anti-tumor proliferation and prevention of tumor drug resistance, the anti-cancer effect can be exerted.
Angiogenesis plays an important role in the treatment of liver cancer
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The three pathways of VEGF, FGF and PDGF all play a role in it
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Lenvatinib can also reverse the immunosuppressive tumor microenvironment, and cooperate with PD-1 monoclonal antibody to fight tumors
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Figure 5.
The unique mechanism of action of lenvatinib NK cells are an important part of the anti-tumor innate immune response, lenvatinib enhances anti-tumor immunity by promoting the activation and infiltration of NK cells
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The mechanism lies in: On the one hand, lenvatinib improves the tumor infiltration ability of NK cells by regulating the expression of adhesion molecules and chemokines
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On the other hand, lenvatinib enhances the cytotoxicity of NK cells by up-regulating the expression of natural killer receptors CD16 and NKp46 on the surface of NK cells
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Professor Liu Xiufeng said that lenvatinib has immunomodulatory activity, and the combined immunotherapy achieves a 1+1>2 synergistic effect
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Lenvatinib combined immunotherapy has entered the clinic, and various studies are on the way
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Finally, Professor Qin Shukui, the chairperson of the conference, mentioned in the summary: “As a new type of targeted drug, lenvatinib has made important breakthroughs in the treatment of liver cancer by its single-drug or combined drug model, and has also accumulated a solid evidence-based medicine.
Evidence has become the standard treatment option for unresectable HCC at home and abroad
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And clinical trials for other malignant solid tumors are also being carried out in various places.
It has superior development prospects and potential in the field of tumor treatment
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"In addition, we are also delighted.
It can be seen that starting March 1, 2021, lenvatinib has implemented a new round of medical insurance prices, which will greatly reduce the economic burden of liver cancer patients in China
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Here, I also hope that Eisai China Pharmaceutical will not forget its original aspiration, move forward, and continue to work with medical professionals to further meet the treatment needs of Chinese patients! "Eisai CSCO Enterprise Cloud Showroom* This article is only used to provide scientific information to medical professionals, and does not represent the views of this platform