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The 25th National Congress of Clinical Oncology and the 2022 CSCO Academic Annual Conference were held from November 5 to 12, 2022, on the occasion, the Chinese Society of Clinical Oncology and Yimaitong jointly launched the "CSCO First Live Room - Food in Wo, Protect the Stomach" big coffee interview column.
This paper aims to explore the standardized diagnosis and treatment practice and clinical hot topics
of digestive system tumors.
Professor Liang Han of Tianjin Medical University Cancer Hospital was invited to host the live broadcast room, and Professor Guo Qingqu from the Department of Gastrointestinal Surgery of the Second Affiliated Hospital of Zhejiang University School of Medicine, Professor Li Wei from the Department of Oncology of the First Affiliated Hospital of Soochow University and Professor Zhu Xiaodong from the Department of Medical Oncology of Fudan University Cancer Hospital were invited Three leaders in the field of gastrointestinal tumors served as guests to discuss the research progress and future treatment trends
of digestive tumor immunotherapy.
Upper gastrointestinal tumor immunotherapy has entered the era of "three perfections"
The advent of immunotherapy has injected new vitality into digestive tumors such as esophageal cancer and gastric cancer, and has a broader clinical prospect than chemotherapy due to its long duration and low susceptibility¹
。 In recent years, CheckMate-649, CheckMate-577 and CheckMate-648 research have appeared in major international conferences, and upper gastrointestinal tumor immunotherapy has gradually entered the "three-complete" era
of all positions (gastric cancer, esophageal cancer, gastroesophageal junction cancer), all types (squamous cell carcinoma, adenocarcinoma), and the whole course of the disease (adjuvant therapy, advanced first-line, and advanced posterior line).
The latest research progress and breakthrough in upper gastrointestinal tumor immunotherapy?
Professor Li Wei
In terms of first-line treatment of advanced gastric cancer, nivolumab is the first immunotherapy drug
approved for the first-line population-wide indication of advanced gastric cancer in China.
CheckMate-649 is the largest phase III study of first-line immunotherapy for advanced gastric cancer with the longest follow-up time, and its efficacy has been fully verified
.
The 2022 ESMO GI newly released 2-year follow-up results of the Chinese subgroup showed that nivolumab plus chemotherapy significantly improved overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR)²
compared with chemotherapy, regardless of PD-L1 CPS≥5 population or all randomized (ITT) populations.
In addition, the ORIENT-16 study also showed that the combination regimen of sindilimab brought benefits to the whole population of advanced gastric cancer in China³.
Therefore, the 2022 CSCO gastric cancer guidelines recommend the combination of immunization regimen as the first-line population for advanced gastric cancer⁴
.
Figure 1: OS, PFS, ORR, and DOR in PD-L1 CPS≥5 and ITT populations in the nivolumab plus chemotherapy group versus chemotherapy group
In addition to HRE2-negative people, the progress of immunotherapy in other gastric cancer people is also worth paying attention to
.
The KEYNOTE-062 study demonstrated the survival benefit of PD-1 monoclonal antibody in MSI-H populations for the first time⁵
.
This is followed by HRE2-positive patients, and KEYNOTE-811 studies suggest that anti-HER2 therapy with immune checkpoint inhibitors may be a potential combination strategy⁶
.
Finally, there is the Claudin18.
2-positive population, and CAR-T cell therapy research around this target is also ongoing⁷
.
In the field of esophageal cancer, multiple phase III studies⁸⁻¹³, including CheckMate-648, have fully confirmed the standard of
care for immunotherapy combined with chemotherapy in the first-line treatment of esophageal cancer.
In the perioperative treatment stage of gastric cancer and esophageal cancer, radiotherapy and chemotherapy are still the standard treatment, but neoadjuvant immunotherapy and postoperative adjuvant immunotherapy are also exploring new breakthroughs
.
The biggest breakthrough was the CheckMate-577 study, which demonstrated for the first time that nivolumab monotherapy for esophageal and gastroesophageal junction cancer can confer a doubling of disease-free survival (DFS) benefits¹⁴
.
Professor Liang Han
Immunotherapy has brought earth-shaking changes to the field of upper gastrointestinal tumors, from the first line of advanced gastric cancer to postoperative adjuvant therapy for esophageal cancer, and then to the exploration of neoadjuvant immunotherapy in recent years, the status of immunotherapy is constantly escalating
.
Immunotherapy opens up a new pattern of upper gastrointestinal tumors
Immunotherapy has achieved fruitful results in the field of gastric cancer, starting from the back line and gradually advancing to the front line, and now immunotherapy combined with chemotherapy has become the standard treatment of the first line of advanced gastric cancer, following chemotherapy and targeting, advanced gastric cancer ushered in a new treatment pattern
of immunotherapy.
According to the latest guideline recommendations and clinical research results, how is gastric cancer immunotherapy laid out?
Professor Zhu Xiaodong
In the first-line treatment of advanced gastric cancer, nivolumab combined with chemotherapy helped HER2-negative people achieve a breakthrough in survival, and was recommended
by the 2022 CSCO gastric cancer diagnosis and treatment guidelines as the first-line population.
The population-wide recommendation is based on the fact that CheckMate-649 not only met the dual primary endpoints of OS and PFS in the PD-L1 CPS≥5 population, but also studied the endpoints, including the PD-L1 CPS≥1 population and the OS of all populations were involved in the allocation of α values, so this endpoint was also statistically significant
.
In addition, the bright data of nivolumab in first-line therapy provides a new idea
for the conversion therapy of advanced gastric cancer.
For HER2-positive people, the strategy of immune combined with targeted therapy has been listed as a Level III recommendation
based on the KEYNOTE-811 study.
For people with dMMR, pembrolizumab first-line therapy is listed as a level II recommendation, and nivolumab plus FOLFOX/XELOX first-line therapy is listed as a level III recommendation
.
Finally, in the third-line treatment of advanced gastric cancer, nivolumab monotherapy showed OS benefit in the whole population in the ATTRACTION-02 study and was listed as a Class I recommendation⁴
.
Professor Liang Han
From the update of the 2022 CSCO gastric cancer diagnosis and treatment guidelines, it can be seen that immunotherapy has a layout in multiple lines of gastric cancer, and the gastric cancer immunotherapy model is becoming more and more rich and individualized
.
The primary endpoints of the CheckMate-649 study were OS and PFS in the CPS≥5 population, but many countries such as China, the United States, and Japan approved nivolumab combined with chemotherapy for the first-line population-wide indication for advanced gastric cancer based on the secondary study endpoint, that is, OS in all populations, and international and domestic guidelines also consistently recommend the whole population
.
In the real world, PD-L1 testing still has the problems of clinical inaccessibility, high cost, and inconsistent clinical thresholds, and nivolumab brings new therapeutic hope
to patients who cannot be tested for PD-L1.
The future of conversion therapy in the era of immunity can be expected
With the advent of immune drugs, patients with advanced gastric cancer have the possibility
of long-term survival.
In addition, some patients with unresectable advanced gastric cancer may still be converted to a resectable state through conversion therapy and obtain a glimmer of
life.
At present, conversion therapy is still being explored, and immune-based conversion therapy can be expected
in the future.
Exploration of immunotherapy in conversion therapy for advanced gastric cancer and esophageal cancer?
Professor Guo Qingqu
The concept of conversion therapy was first proposed by Bismuth et al.
¹⁵ in the treatment of colorectal cancer liver metastasis in 1996 and achieved good results, and this concept was then introduced into the treatment of advanced gastric cancer, which is defined as the surgical resection
of R0 by effective preoperative treatment such as chemotherapy, radiotherapy, targeting, immunotherapy and other effective preoperative treatment in patients with initial unresectable locally advanced or distant metastases 。 According to the biological behavior of gastric cancer, Japanese scholars Yoshida et al.
¹⁶ divided stage IV.
gastric cancer into four types: type I is potentially resectable, type II is borderline resectable, type III is potentially unresectable, and type IV is extensive metastasis
.
It is generally accepted that preoperative chemotherapy in type I patients can be classified as a concept of neoadjuvant chemotherapy
.
The indications for conversion therapy are mainly type II patients, including some type III and a very small number of type IV patients
.
Conversion therapy considers tumor metastasis and focuses on the efficacy and safety
of conversion regimens.
Nivolumab in combination with chemotherapy has excellent efficacy and good tolerability in first-line treatment of advanced gastric cancer in China, and may be considered as a potential translational regimen
.
Professor Liang Han
Stage IV gastric cancer is a systemic disease that requires the rational use of a variety of different treatment methods for comprehensive treatment, and clinical practice has indeed seen that some patients with stage IV gastric cancer have significantly improved their prognosis
by obtaining R0 surgery opportunities through conversion therapy.
The ORR of nivolumab combined with chemotherapy in CheckMate-649 in the first-line treatment of advanced gastric cancer in China is close to 70%², and immunotherapy has a tailing effect and good safety, so the immune-based conversion regimen can be expected
in the future.
epilogue
Professor Liang Han
The global and Chinese burden of gastrointestinal tumors is still very heavy, and the development of immunotherapy has brought new opportunities for gastrointestinal tumors and changed the pattern
of gastrointestinal tumor treatment.
However, immunotherapy has developed rapidly in recent years, and we still face many clinical problems, such as the exploration of perioperative immunotherapy and the improvement of standardized diagnosis and treatment, which require us to continuously improve and optimize in order to achieve the goal of "Healthy China 2030" as soon as possible
.
Professor Liang Han
Director of Gastric Cancer Center, Cancer Hospital of Tianjin Medical University
Director of the Chinese Anti-Cancer Association
Chairman of the Gastric Cancer Professional Committee of the Chinese Anti-Cancer Association
Chairman-elect of the Cancer Surgery Professional Committee of the Chinese Medical Doctor Association
Vice Chairman of the Gastric Cancer Expert Committee of the Chinese Society of Clinical Oncology
Vice Chairman of the Gastrointestinal Stromal Tumor Professional Committee of the Chinese Anti-Cancer Association
Deputy leader of the Gastroenterology Group of the Oncology Society of the Chinese Medical Association
Member of the Standing Committee of the Integrative Medicine Professional Committee of the Chinese Anti-Cancer Association
Member of the National Expert Committee for Standardized Diagnosis and Treatment of Tumors of the Ministry of Health
Chairman of the Gastric Cancer Professional Committee of Tianjin Anti-Cancer Association
Executive Deputy Editor of Chinese Clinical Oncology
The first Tianjin famous doctor
Selected as Elsevier's 2021 China Highly Cited Scholar
Selected into the 2021 China Cancer Research Expert Nomination List "Research" Value Peak Award
Professor Guo Qingqu
Doctor of Medicine, Chief Physician and Master Supervisor of the Second Affiliated Hospital of Zhejiang University
Vice Chairman of the Youth Committee of Gastric Cancer Surgery Group of Zhejiang Anti-Cancer Association
Member of the Standing Committee of Zhejiang Provincial Mathematical Medicine Gastric Cancer Professional Committee
Member of the Standing Committee of the National Cardia Cancer Professional Committee of the Chinese Society of General Practitioners
Member of the Professional Committee of Gastrointestinal Stromal Tumors of Zhejiang Anti-Cancer Association
Member of the Gastroenterology and Nutrition Support Group of the Society of Parenteral Parenteral Nutrition of Zhejiang Medical Association
Member of the Cancer Nutrition Pathway Group of the Tumor Nutrition and Supportive Treatment Professional Committee of the Chinese Anti-Cancer Association
Reviewer for international journals such as Biochem Pharmacol, Plos one and Cytopathology
His research interests include clinical and basic research on gastric cancer (surgical treatment, chemotherapy, nutritional therapy)
He has presided over 4 projects of the National Natural Science Foundation of China and provincial and ministerial scientific research projects
He is good at individualized treatment of gastrointestinal tumors, especially minimally invasive surgical treatment of gastric cancer, chemotherapy, targeted and immunocomprehensive therapy and perioperative nutritional therapy for gastric cancer, and carries out related treatment of gastrointestinal stromal tumor, intestinal fistula and intestinal obstruction
Professor Li Wei
Deputy Director of the Department of Oncology, First Affiliated Hospital of Soochow University
Doctor of Medicine, Deputy Chief Physician, Associate Professor, Master Supervisor
Member of the Pancreatic Cancer Expert Committee of the Chinese Society of Clinical Oncology (CSCO).
Member of the Young Expert Committee of the Chinese Society of Clinical Oncology (CSCO).
Youth member of the Cancer Nutrition Professional Committee of the Chinese Anti-Cancer Association
Youth member of the Integrated Oncology Committee of Traditional Chinese and Western Medicine of the Chinese Anti-Cancer Association
Young member of the Colorectal Oncology Professional Committee of the Chinese Medical Doctor Association
Youth Committee Member of Cancer Chemotherapy and Biological Therapy Branch of Jiangsu Medical Association
Youth Committee Member of Internal Medicine Branch of Jiangsu Medical Association
Member of Cancer Rehabilitation and Palliative Care Professional Committee of Jiangsu Anti-Cancer Society
Youth member of Pancreas Professional Committee of Jiangsu Anti-Cancer Society
Youth member of the Cancer Nutrition Professional Committee of Jiangsu Anti-Cancer Society
Member of the Tumor Immunology Professional Committee of Jiangsu Society of Immunology
Young member of the Professional Committee of Precision Treatment of Hepatobiliary Diseases of Jiangsu Research Hospital Association
Member of the Oncology Branch of Suzhou Medical Association, academic secretary, and vice chairman of the Youth Committee
Director of Suzhou Anti-Cancer Association
He has presided over 3 National Natural Science Foundation of China and published more than 50 SCI papers
Jiangsu Province "Six Talent Peaks", "333 Talents", "Science and Education Strong Health Young Medical Talents"
Young Investigator's Award
Professor Zhu Xiaodong
Chief physician of the Department of Medical Oncology, Fudan University Cancer Hospital, and tutor of master's students
Mainly engaged in the comprehensive treatment of digestive tract tumors, his research direction is the mechanism of drug resistance and efficacy prediction of digestive tract tumors
He has presided over the completion of Fudan Youth Fund, Shanghai Natural Science Foundation, co-completed several National Natural Science Foundations, and participated in the completion of many major national projects
Member of the Tumor Targeted Therapy Professional Committee of the Chinese Anti-Cancer Association
Vice Chairman of Hereditary Gastrointestinal Tumors Professional Committee of Shanghai Anti-Cancer Association
Member of the Standing Committee of the Tumor Biotherapy Professional Committee of Shanghai Anti-Cancer Association
Vice Chairman of the Colorectal Special Committee of the Oncology Branch of Shanghai Association of Social Medical Institutions
Director of China Soong Ching Ling Foundation for Cancer Care and Industry-University-Research Alliance
Member of the Abdominal Cancer Professional Committee of the Chinese Medical Education Association
Member of the Cancer Nutrition and Chemotherapy Group of the Cancer Nutrition and Supportive Treatment Professional Committee of the Chinese Anti-Cancer Association
Member of Gastrointestinal Oncology Professional Committee of Shanghai Anti-Cancer Association
Member of the Cancer Rehabilitation and Palliative Care Professional Committee (CRPC) of Shanghai Anti-Cancer Association
Member of the editorial board of Annals of Oncology Excerpts China Edition (GI Tumors).
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ESMO World Congress on Gastrointestinal Cancer 2022 Abstr P-86.
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Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial.
JAMA.
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doi: 10.
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1506-CN-2202844
Edited by Dreams
Revised: Fish balls
Typesetting: Wanderer
Execution: Traveler
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