On June 6, 2024, the results of the phase II NEOCAP study led by the team of Ding Peirong, Pan Zhizhong, Zhang Xiaoshi and Tang Jinghua from the Sun Yat-sen University Cancer Center were published in The Lancet Oncology, a top international oncology journal. This study is the first in the world to report organ preservation therapy after immunotherapy for locally advanced colon cancer with mismatch repair deficiency (dMMR) or microsatellite instability (MSI-H), providing important evidence-based medical evidence for a new strategy for organ preservation therapy for dMMR/MSI-H locally advanced colorectal cancer.
In recent years, PD-1 antibody has shown significant efficacy in the neoadjuvant treatment of patients with dMMR/MSI-H locally advanced colorectal cancer, with a pathological complete response rate of 60%~65%. Previous studies have shown that watchful waiting therapy for patients with complete remission after neoadjuvant immunotherapy for dMMR/MSI-H rectal cancer can avoid chemoradiotherapy and surgery, and the long-term oncology outcome is satisfactory. However, there is no research evidence on whether organ preservation is feasible for dMMR/MSI-H colon cancer, which is larger in populations. In fact, these patients are young, have a high proportion of multiple primary tumors, and also have a strong need to preserve organ function, reduce surgical trauma, and improve survival rates, so there is a great need to explore the feasibility of new treatment modalities. On the other hand, previous studies have shown that anti-angiogenic small molecule drugs can modulate the local microenvironment of tumors and improve the efficacy of PD-1 antibodies, but they have not been verified in prospective studies.
Based on the above background, the team of Peirong Ding, Zhizhong Pan, Xiaoshi Zhang, and Jinghua Tang led an open-label, single-arm, phase II clinical study of camrelizumab combined with apatinib in dMMR/MSI-H locally advanced colorectal cancer, aiming to explore the efficacy and safety of the combination therapy regimen, as well as the feasibility of organ preservation in this population.
Between September 2020 and December 2022, a total of 53 patients were included in the study, of which 52 patients were included in the final efficacy analysis. The primary endpoint of the study was complete response rate (pathological complete response rate + clinical complete response rate). Secondary endpoints included objective response rate, 3-year recurrence-free survival and overall survival, safety, and more.
Research flowcharts
The results of the study showed that the complete response rate in this cohort was 73%, with 28 patients (54%) achieving a complete clinical response and 24 patients adopting a watchful waiting organ preservation strategy. None of these patients experienced tumor regrowth after a median follow-up of 11.2 months. In terms of safety, the incidence of grade 3 and above adverse events in the study was 38%, and one patient died due to immune-related hepatitis. The results of this study show that anti-PD-1 combined with anti-angiogenic neoadjuvant therapy has excellent efficacy in dMMR/MSI-H locally advanced colorectal cancer. More importantly, in addition to rectal cancer, organ preservation in patients with dMMR/MSI-H colon cancer after achieving complete clinical remission with neoadjuvant immunotherapy is safe and feasible.
Waterfall plot of tumor regression ratio on radiograph
This study is the world's first prospective clinical study of watchful waiting for organ preservation after neoadjuvant immunotherapy for locally advanced colon cancer with dMMR/MSI-H. This study provides important evidence-based medical evidence for organ function preservation in patients with dMMR/MSI-H colon cancer, which is expected to change the treatment landscape of this type of cancer, and demonstrates the leading position of the colorectal cancer research team in the clinical research of colorectal cancer immunotherapy.
丁培荣、潘志忠、张晓实、唐京华团队长期致力于dMMR/MSI-H结直肠癌、遗传性结直肠癌以及年轻肠癌发病机制和免疫治疗耐药机制研究。 团队围绕结直肠癌的精准分型和免疫治疗策略开展了一系列研究，并取得了丰硕的成果，发表于The Lancet Oncology、Nature Communications、Journal of the National Comprehensive Cancer Network、EBioMedicine、Journal of the National Cancer Institute、Journal for Immunotherapy of Cancer、European Journal of cancer等国际知名期刊。
Professor Ding Peirong, Professor Pan Zhizhong, Deputy Chief Physician Tang Jinghua and Professor Zhang Xiaoshi of the Department of Biological Therapy are the co-corresponding authors of the paper, and Dr. Yu Jiehai, attending physician Xiao Binyi, deputy chief physician Jiang Wu and Li Dandan of the Department of Biological Therapy are the co-first authors of the paper.
Brief description of the principal investigator
Ding Peirong
Corresponding author
Director of the Department of Colorectal Medicine, Sun Yat-sen University Cancer Center, Professor, Chief Physician, Doctoral Supervisor. He is one of the first batch of outstanding young medical talents in Guangdong Province, a clinical medical scientist of Sun Yat-sen University, a fellow of the American College of Surgeons (FACS), and a visiting scholar at Sloan Kettering Memorial Cancer Center. He has presided over many projects such as the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, the Guangzhou Science and Technology Program, and the 5010 Project of Sun Yat-sen University. His main research interests include molecular screening and immune heterogeneity of hereditary colorectal cancer, sensitivity prediction and strategy optimization of neoadjuvant therapy for rectal cancer based on multi-omics technology. As a corresponding author (including co-author), he has published more than 40 papers in journals such as Lancet Oncol, Cell Res, Nat Commun, J Natl Cancer I, Ann Surg, EBioMedicine, J Natl Compr Canc Ne, J Immunother Cancer, Int J Cancer, Eur J Cancer, etc. He is a member of the expert group of experts on clinical diagnosis, treatment and family management of hereditary colorectal cancer, Chinese expert consensus on the diagnosis and treatment of lateral lymph node metastasis of rectal cancer (2019 edition), expert consensus on waiting observation strategy after neoadjuvant therapy for rectal cancer, and consensus expert group on clinical operation of MDT for colorectal cancer liver metastasis. Vice Chairman of the Family Hereditary Tumor Professional Committee of the Chinese Anti-Cancer Association; Vice Chairman of the Young Expert Committee of the Chinese Society of Clinical Oncology (CSCO); Chairman of the Hereditary Tumor Professional Committee of Guangdong Anti-Cancer Association; Vice Chairman of the Gastroenterology Branch of Guangdong Medical Association; Vice Chairman of the Colorectal Genetics Committee of the Chinese Medical Doctor Association.
Pan Zhizhong
Co-corresponding author
Doctor of Medicine, Professor, Chief Physician, Doctoral Supervisor. Director of the Department of Colorectal Medicine, Sun Yat-sen University Cancer Center, Chief Expert of Colorectal Cancer Surgery, and Director of the Laparoscopic Surgeon Training Base of the Chinese Medical Doctor Association. He is the vice chairman of the Tumor Surgery Committee of the Chinese Research Hospital Association, the vice chairman of the Tumor Metastasis Committee of the Anorectal Physician Branch of the Chinese Medical Doctor Association, the vice chairman of the Digestive Oncology Comprehensive Diagnosis and Treatment Branch of the China Association for the Promotion of International Exchange in Health Care, the vice chairman of the Tumor Prevention and Treatment Professional Committee of the Guangdong Health Management Association, and the Fellow of American College of Surgeons (FACS). Chairman of the Chinese Colorectal Cancer MDT Alliance. He has undertaken 3 national projects, 2 provincial and ministerial fund projects, and published more than 200 professional papers. As a major participant, he won the first prize of the Science and Technology Award of the Chinese Medical Association and the first prize of the Guangdong Science and Technology Progress Award.
Zhang Xiaoshi
Co-corresponding author
Doctor of Medicine, Professor, Chief Physician. Deputy Director of the Biological Therapy Center of Sun Yat-sen University Cancer Prevention and Treatment Center, Chief Expert of Melanoma Single Disease. He is the honorary chairman of the Melanoma Committee of the Guangdong Anti-Cancer Association, the chairman of the Tumor Immunotherapy Committee of the Guangdong Clinical Medical Association, and the vice chairman of the Melanoma Committee of the Chinese Society of Clinical Oncology (CSCO). He has published many high-level papers as a corresponding author, including Cell research, Nature communications, Eur J Cancer, Front Immunol, etc., presided over 3 projects of the National Natural Science Foundation of China, 5 provincial scientific research projects, and edited and published monographs such as "Tumor Biotherapeutics", "Basic and Clinical Melanoma" and "Melanoma".
Tang Jinghua
Co-corresponding author
Doctor of Medicine, Deputy Chief Physician, Master's Supervisor. He is a member of the Hereditary Bowel Cancer Working Group of the Cancer Prevention and Treatment Center of Sun Yat-sen University, a member of the Gastrointestinal Surgery Youth Committee of the Guangdong Medical Association, and a member of the Gastrointestinal Tumor Branch of the Guangdong Precision Medicine Application Society. He is mainly engaged in the comprehensive treatment of colorectal cancer and related research, with research interests in colorectal cancer surgery, individualized anus preservation, neoadjuvant therapy and immunotherapy for colorectal cancer.
Correspondents: Sun Yat-sen University Cancer Center Zhao Xianting, Chen Jun, Wen Chaoyang, Zhou Xinxi