Editor's note: [Expert Group Draft] With ingenuity, respect the original intention. Professor Cao Xinping of the Cancer Center of Sun Yat-sen University is the executive editor-in-chief, and experts in the field of radiotherapy are invited to share their academic views, a total of 2 issues for exchange.
Second installment
Executive Editor-in-Chief: Professor Cao Xinping
Title: Advances in ADC drug therapy for cervical cancer
Authors: Cao Xinping, Ni Yi, Sun Yat-sen University Cancer Center/Zhejiang Cancer Hospital
Expert Profile
Prof. Xinping Cao
Sun Yat-sen University Cancer Hospital
Doctor of Medicine, Chief Physician, Attending Professor, Clinical PI, Postdoctoral Cooperative Supervisor
Member of the Board of Directors of the Chinese Anti-Cancer Association
Chairman of the Brachyradiotherapy Committee of the Chinese Anti-Cancer Association
Deputy head of the brachytherapy group of the Radiation Oncology Branch of the Chinese Medical Association
Deputy head of the brachytherapy group of the Chinese Medical Doctor Association
Member of the Cervical Cancer Quality Control Committee of the National Cancer Center of the National Cancer Center
Academic expert of the Gynecologic Oncology Group of the Precision Medicine and Oncology MDT Professional Committee of the Chinese Association of Research Hospitals
Leader of the brachytherapy group of Guangdong Radiation Oncology Branch of Chinese Medical Association
Vice Chairman of the Gynecologic Tumor MDT Special Committee of Guangdong Health Management Society
Vice Chairman of the Radiation Therapy Branch of Guangzhou Anti-Cancer Association
Visiting Professor, Peking University Health Science Center
Ni Engraved
Deputy Chief Physician of the Department of Gynecologic Oncology and Radiation Oncology of Zhejiang Provincial Cancer Hospital
He is a young member of the Brachytherapy Professional Committee of the Chinese Anti-Cancer Association
Youth member of the Gynecologic Oncology Branch of Zhejiang Medical Association
Visiting scholar at Japan Cancer Institute Ariake Hospital
However, for patients with advanced disease, recurrent and metastasized, the limited treatment mode and high recurrence rate often lead to poor prognosis, and the survival of patients needs to be improved urgently. Following the era of chemotherapy, targeted and immunization, ADC drugs conjugated with cytotoxic drugs and targeted monoclonal antibodies have opened up the era of fourth-tier drug treatment for tumors. It brings more hope to patients with recurrent, metastatic and advanced cervical cancer.
One
Mechanism of action of ADC drugs
The structure of an ADC generally consists of three parts:
Antibody: Generally a specific monoclonal antibody designed against a target antigen on the surface of tumor cells
Cytotoxic payload (drug): highly active cytotoxin
Linker: Enables a covalent bond between a toxin and an antibody to be stably clicked
ADC drugs, also known as missile drug therapy, recognize antibodies + linkers + toxic warheads, identify antibodies to find cancer cells, cancer cells engulf ADC drugs, and toxic warheads are released in cancer cells to kill cancer cells.
Two
Application of ADC drugs in cervical cancer
1、innovaTV 204/GOG-3023/ENGOT-cx6研究
Results: The ORR of TV monotherapy was 24%, including a CR7%. This is the efficacy of the first ADC drug for cervical cancer, and the efficacy has improved to a certain extent.
2 ENGOT-Cx8/GOG-3024/innovaTV 205:Tisotumab vedotin (TV)
Due to the limited efficacy of single agents, the efficacy of TV combined with other drugs in the treatment of cervical cancer has been improved to a certain extent, but the side effects have also been improved to a certain extent, and the complete remission rate has not increased significantly. Therefore, the efficacy needs to be further improved.
3. C018 study (CTR20211602), this study is a phase II clinical study of RC48-ADC drug
Results: The ORR was 43.8% and the CR was 0, but the Her-2 was always positive, and the proportion of Her-2 positive in cervical cancer patients was about 50%. Therefore, only half of the patients were able to use the RC48-ADC drug.
4、DESTINY-PanTumor02：T-DXd治疗HER2表达实体瘤患者
Results: T-DXd had an ORR of 50% (Her-2-positive patients) and a CR rate of 5%, and the efficacy was also improved.
At present, TV, RC-48, T-Dxd, etc. have achieved good efficacy in clinical studies of recurrent advanced cervical cancer. As ADC drugs have become a research hotspot in the field of cervical cancer, the importance and urgency of understanding the mechanism behind ADC drugs has gradually become prominent, and it is expected that more basic scientific explorations in the future can make ADC drugs better serve the clinical practice. At the same time, the economics and accessibility of ADC drugs need to be improved, and their clinical safety remains to be observed for a long time. It is believed that with the development of innovative technologies, such as the emergence of new linker and site-specific conjugation technologies, these problems will be gradually solved, and it is expected that in the near future, ADCs can truly enter the clinic in full scope and benefit patients.
Drafting/Reviewing:
Cao Xinping, Chairman of the Brachyradiotherapy Committee of the Chinese Anti-Cancer Association
Ni Yi, a youth member of the Brachyradiotherapy Committee of the Chinese Anti-Cancer Association
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