Pinnacle Discussion, Focus on the Frontier 2022 ESMO Immunization Frontier Progress Roundtable (Part II)

In recent years, immunotherapy has gained momentum in the treatment of liver cancer, and at the 2022 ESMO Conference, Chinese scholars joined hands to make a strong voice
in China.
On this occasion, Professor Cai Jianqiang of the Cancer Hospital of the Chinese Academy of Medical Sciences, Professor Chen Minshan of the Cancer Prevention and Treatment Center of Sun Yat-sen University, Professor Zhang Boheng of Zhongshan Xiamen Hospital of Fudan and Professor Gao Qiang of Zhongshan Hospital Affiliated to Fudan University were specially invited to form an expert group, and Professor Ye Feng of the First Affiliated Hospital of Xiamen University was invited to interpret the new progress of liver cancer immunotherapy from a new perspective and look forward to the future development direction
of liver cancer immunotherapy.

Highlights of this issue

Systemic and/or topical therapy provide more possibilities for radical resection, reduce postoperative recurrence, and improve prognosis in patients with intermediate and advanced HCC

The "Shuangda" conversion therapy regimen is the first protocol to achieve HCC conversion therapy in combination with macromolecule bevacizumab

Talking about the future of liver cancer: broad alliance, forward front, MDT, biomarker, new targets and new drugs, precision medicine, etc

Target-free conversion therapy is crucial

Professor Ye Feng: The effect of systematic anti-tumor therapy and/or local therapy to control tumors can provide more possibilities
for patients with intermediate and advanced liver cancer to undergo radical resection, reduce postoperative recurrence and improve prognosis.
At this ESMO conference, the research on liver cancer conversion therapy with Chinese characteristics has also entered the international academic stage, how do you see the application of target-free combination in liver cancer conversion therapy?

Prof.
Minshan Chen: Combination immunotherapy is one of the main modalities of conversion therapy for potentially resectable liver cancer1
.
Translational therapy has done a lot of research by Chinese experts and is in a leading position
internationally.
In particular, our academician Fan Jia led the compilation and release of the expert consensus on the conversion therapy of liver cancer, which greatly guided and standardized the conversion treatment of
liver cancer in China.
This ESMO meeting has two reports from our Chinese scholars (Fudan Zhongshan Hospital and West China Hospital), which is indeed encouraging
.
Professor Xu Li of our center uses hepatic arterial perfusion chemotherapy (HAIC) combined with sindilimab for the treatment of patients with advanced and potentially resectable HCC with high surgical conversion rates, and patients who undergo conversion surgery have excellent PFS of 15.
7 months2, which fully demonstrates that local therapy combined with systemic therapy is a feasible strategy
for conversion therapy in patients with intermediate and advanced HCC.
The development of conversion therapy has greatly promoted the formation of a multidisciplinary diagnosis and treatment model for liver cancer in China, and MDT can be used as a cohesive
force for the treatment of liver cancer.

Fig.
1 Efficacy of HAIC+ sindilimab conversion therapy

Liver cancer transformation therapy research continues to make breakthroughs

Prof.
Ye Feng: Could you please talk about the efficacy and safety study of sindilimab combined with bevacizumab biosimilar ("Shuangda" combination) as a conversion therapy led by Academician Fan Jia and Professor Sun Huichuan, and the translational research exploration of TACE+ lenva/sola versus TACE alone for initial unresectable HCC conducted by Professor Wen Tianfu's team?

Professor Gao Qiang: The ORIENT-32 study achieved gratifying results and was approved as the first-line treatment
for unresectable liver cancer in China.
The results of the exploration of the first immune combined antiangiogenic therapy regimen for conversion therapy in patients with medium-term (BCLC stage B) HCC showed that the conversion rate of the "Shuangda" combination was as high as 56.
7%3, which provided a new option
for conversion therapy for patients with unresectable liver cancer.
The mechanism of targeted immunity + interventional therapy is complementary, so it also has a high surgical conversion rate4
.
It is believed that in the future, liver cancer treatment programs with Chinese characteristics, such as targeted immune therapy combined with interventional therapy/radiotherapy, can greatly increase the proportion of
liver cancer conversion therapy population.

Fig.
2 Efficacy of sindilimab + bevacizumab analogue conversion therapy

Future exploration direction of liver cancer treatment

Prof.
Ye Feng: Based on today's discussion and other recent research advances in the field, could you please talk about the clinical application prospects of immunotherapy, targeted immunotherapy and other therapies in the future? In the field of liver cancer, what new directions need to be further explored in the future?

Prof.
Cai Jianqiang: Targeted immunization therapy has brought hope to HCC patients, but liver cancer treatment has a long
way to go.
In the future, liver cancer treatment should play a "combination box", widely combine HAIC/TACE, targeted, immune and other treatment methods, and actively carry out translational therapy research
.
At the same time, with the continuous advancement of systemic therapy, the prospect of immune combination regimens in neoadjuvant and adjuvant therapy is promising5,6, which is worth exploring
in depth.
In addition, it is necessary to place great emphasis on MDT and use the comprehensive diagnosis and treatment methods of MDT to formulate the most optimal and effective treatment plan
for liver cancer.

Forge ahead and seize the opportunities of life

Prof.
Ye Feng: What do you think is the clinical application prospect of immunotherapy, targeted immunotherapy and other therapies in the future? In the field of liver cancer, what new directions need to be further explored in the future?

Professor Zhang Boheng: In the field of liver cancer, it is necessary to deeply explore biomarkers in the future and predict tumor prognosis or tumor efficacy through peripheral blood or histology detection; Actively explore new targets of liver cancer immunotherapy, such as SOAT1, a new target of the "metabolism-driven" subtype of liver cancer, and CCR4, a new target of liver cancer immunotherapy7,8; continue to break through new immune drugs, such as ADCC, CAR-T cells, oncolytic viruses, etc.
; Focus on precise typing and individualized treatment, such as dynamic detection of tumors through tumor spatiotemporal omics research to guide clinical practice
.

summary

Through continuous exploration and practice, immunotherapy has entered the front line from the back line to the first line, expanded from late stage to early stage, gradually covered a wide range of people, and continuously innovated
the treatment pattern of liver cancer.
In this roundtable party, 5 experts took the latest frontier progress of ESMO Conference as the core, expressed their views on hot issues in liver cancer treatment, and talked freely about the current situation and future development direction
of liver cancer treatment.
In the future, clinicians still need to work tirelessly, up and down, and work together to build a road of liver cancer diagnosis and treatment with Chinese characteristics!

Experts in this issue

Professor Cai Jianqiang

Deputy Director of the National Cancer Center

Vice President, Chief Physician and PhD Supervisor of Cancer Hospital of Chinese Academy of Medical Sciences

The National Health Commission has made outstanding contributions to young and middle-aged experts

Member of the Surgical Branch of the Chinese Medical Association

Professor Chen Minshan

Director of the Department of Liver Surgery, Sun Yat-sen University Cancer Center for Cancer Prevention and Treatment

Director of the Institute of Liver Cancer, Sun Yat-sen University

Chairman of the Liver Cancer Professional Committee of the Chinese Anti-Cancer Association

Vice Chairman of the Liver Cancer Professional Committee of the Chinese Medical Doctor Association

Prof.
Boheng Zhang

Chief physician, doctoral supervisor of oncology

Vice President of Fudan Zhongshan Xiamen Hospital and Director of Department of Hepato-Oncology

He is also the deputy director of the Center for Evidence-Based Medicine of Fudan University

Member of the Standing Committee of the Clinical Disease and Evidence-Based Medicine Professional Committee of the Chinese Medical Association

Professor Gao Qiang

Chief physician and doctoral supervisor of the Department of Liver Surgery, Zhongshan Hospital, Fudan University

Director of the Office of the Institute of Liver Cancer of Fudan University

Changjiang Scholars Award Program "Distinguished Professor"

10,000 people plan, national excellent youth, national youth post experts

Prof.
Ye Feng

Chief physician, Ph.
D.
, associate professor of Xiamen University

Administrative Director of the Department of Medical Oncology, The First Affiliated Hospital of Xiamen University

Director of the Chinese Society of Clinical Oncology (CSCO).

Member of the Clinical Research Expert Committee of the Chinese Society of Clinical Oncology (CSCO).

References:
1.
Chinese Expert Consensus on Translational Therapy for Liver Cancer (2021 Edition).
2.
Xu Li, et al.
2021 ILC.
3.
H.
Sun, et al.
2022 ESMO ABSTRACT 711P.
4.
Z.
Xiaoyun, et al.
2022 ESMO ABSTRACT 715P.
5.
Kaseb AO, et al.
2020 ASCO ABSTRACT 4955.
6.
Yang XR.
2021 ESMO ABSTRACT 944P.
7.
Jiang Y, et al.
Nature.
2019; 567(7747):257-261.
8.
Gao Y, et al.
J Hepatol.
2022 Jan; 76(1):148-159.