Professor Chin Lun Xiu: Evidence-based and comprehensive layout, the cornerstone of the treatment of liver cancer by lenvatinib is solid

Primary liver cancer is one of the most common malignant tumors in the digestive system, which has the characteristics of high morbidity and mortality, and has long been a global problem

Professor Chin Lun So

Chief Physician, Ph.

• Director of Surgery of Huashan Hospital Affiliated to Fudan University / Executive Vice President of North Hospital

• Director of the Institute of Tumor Metastasis of Fudan University

• He was awarded the National Jieqing, Yangtze River Distinguished Professor, and the chief of 973

• Member of the Surgical Branch of the Chinese Medical Association

• Chairman of the Tumor Precision Treatment Committee of the Chinese Anti-Cancer Association / Honorary Chairman of the Tumor Metastasis Committee

• Vice Chairman of the Expert Committee of Biliary Tumor of the Chinese Society of Clinical Oncology

• Vice President of The Digestive Surgery Branch of the Chinese Association of Research Hospitals

• Editorial board member of Clin Exp Metastasis, Neoplasia and other magazines

• He won the second prize of the National Natural Science Award and the Tan Jiazhen Life Science Award

• Shanghai science and technology elite; Shanghai May Day Labor Medal; Shanghai craftsmen

• He specializes in the surgical treatment of hepatobiliary tumors (more than 400 cases/year of surgery) and the prediction and prevention strategies of tumor metastasis recurrence

With the development of molecular biology, Sorafenib kicked off the HCC molecularly targeted therapy in 2007¹

Since there are still differences between patients enrolled in clinical research and real-world patients, researchers have conducted a number of real-world studies to further verify the efficacy and safety

Although molecularly targeted therapies have made breakthroughs in the field of HCC, there are still some unmet needs
in the clinic.

Professor Qin Lunxiu said that the lack of means and drug resistance to accurately screen the beneficiary population is an unmet need to be solved in the diagnosis
and treatment of HCC.

Tumor cells are known to be very "cunning" and can change under therapeutic stress, leading to drug
resistance.

In addition, there is a certain gap between the efficacy of single-targeted drug therapy and clinical expectations, and there is still room for improvement in
its ORR.

Based on this, clinical researchers continue to explore combination therapy options
based on targeted drugs.

Professor Chin Lun Xiu pointed out that for the formulation of combination therapy regimens, there are three important criteria
for the selection of targeted drugs.

First, effectiveness: HCC develops rapidly, and drugs with more benefits and higher efficiency should be preferred in order to achieve phase-down conversion and transform HCC patients from inoperable to inoperable resection
.

Second, accessibility: Clinicians should prefer drugs that have been included in the health insurance system to reduce the financial burden on patients and provide more benefits
for patients.

Third, safety: give priority to the use of drugs with high safety to ensure the quality of life of
patients during treatment.

Based on the efficacy, safety and economy of lenvatinib, Professor Chin Lunxiu believes that the joint regimen based on lenvatinib is one
of the preferred combination treatment options for HCC in the future.

As the treatment window continues to move forward, renvatinib combined with TACE brings good news to the perioperative treatment of liver cancer patients

Surgical resection is the main treatment for HCC patients to achieve long-term survival and radical cure
.

However, only 20%-30% of patients with confirmed HCC can be removed surgically, and most patients are diagnosed at an advanced stage and have lost the opportunity to operate⁵
.

In recent years, with the continuous emergence of targeted and immune drugs, translational therapy for advanced HCC has ushered in new hopes
.

Patients with advanced HCC can shrink the lesion by targeting combination immunotransformation therapy and undergo surgical resection
after hypothesis.

Professor Chin Lun Xiu said that the existing research shows that the success rate of translational therapy is 20%-30%, which significantly expands the scope of patients treated by surgery and provides more patients with surgical opportunities
.

In addition to the low rate of surgical resection, the high risk of postoperative recurrence of HCC is one of the main challenges currently facing it
.

More than half of patients with HCC have been reported to have relapsed within 5 years of surgery⁶, which is related
to the presence of microdispersed lesions before surgery or a history of hepatitis disease.

In the past, there was a lack of effective adjuvant therapy to reduce the rate of postoperative recurrence, which limited the survival of
patients with HCC.

Today, a number of combinations based on targeted therapy offer new treatment options
to reduce the risk of postoperative HCC recurrence.

Professor Qin Lunxiu introduced that the results of a domestic multi-center LANCE study led by Huashan Hospital of Fudan University showed that for HCC patients with high postoperative recurrence risk, lunvatinib combined with TACE significantly extended the disease-free survival time (DFS) (17 months vs 9 months) compared with TACE alone.
P=0.
0228), which reduced the risk of disease recurrence or death by 40% (HR=0.
6, 95% Cl: 0.
4-1.
0)⁷
.

It can be seen that the joint scheme based on targeted therapy has injected a new "vitality" into HCC treatment, and further extended the survival period
of HCC patients by establishing a whole process management system from preoperative conversion therapy, surgical resection to postoperative adjuvant therapy.

In addition to further exploring combination therapy regimens and perioperative treatment models, the development of liver cancer-specific drugs is also an important direction
for future targeted therapy research on liver cancer.

Professor Qin Lunxiu said that the current targeted therapy drugs for liver cancer are non-specific target inhibitors, which can be applied to a variety of hemangioma species, including liver cancer, but lack liver cancer specificity
.

Future research should explore liver cancer-specific targets, and then develop drugs that target liver cancer-specific targets to help further improve
the survival benefits of liver cancer patients.

In addition, clinical researchers are also exploring the development of multi-target immunotherapy drugs, and there are currently dual-target specific immunotherapy drugs entering clinical research
.

Overall, the road to the development of liver cancer-specific drugs is a long way off, and basic researchers and clinicians will need to work together in the
future.

References:

1.
 Llovet J M, Ricci S, Mazzaferro V, et al.
Sorafenib in advanced hepatocellular carcinoma[J].
New England journal of medicine, 2008, 359(4): 378-390.

2.
 Kudo M, Finn R S, Qin S, et al.
Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial[J].
The Lancet, 2018, 391(10126): 1163-1173.

3.
 Wang D X, Yang X, Lin J Z, et al.
Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China[J].
World Journal of Gastroenterology, 2020, 26(30): 4465.

4.
 Cheon J, Chon H J, Bang Y, et al.
Real-world efficacy and safety of lenvatinib in Korean patients with advanced hepatocellular carcinoma: a multicenter retrospective analysis[J].
Liver Cancer, 2020, 9(5): 613-624.

5.
 Wang P X, Cheng J W, Yang X R.
Detection of circulating tumor cells in hepatocellular carcinoma: applications in diagnosis, prognosis prediction and personalized treatment[J].
Hepatoma Research, 2020, 6: 61.

6.
 Qian X, Zheng H, Xue K, et al.
Recurrence Risk of Liver Cancer Post-hepatectomy Using Machine Learning and Study of Correlation With Immune Infiltration[J].
Frontiers in genetics, 2021: 2554.

7.
 Chen J, Lu L, Wen T F, et al.
945P Adjuvant lenvatinib in combination with TACE for hepatocellular carcinoma patients with high risk of postoperative relapse (LANCE): Updated results from a multi-center prospective cohort study[J].
Annals of Oncology, 2021, 32: S824-S825.

Edit: HCM

Reviewer: Fish balls

Typography: Wanderer

Execution: Traveller