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 of this issue, and experts in the field of cervical cancer are invited to share academic views, a total of 2 issues for exchange.
Phase 1
Executive Editor-in-Chief: Professor Cao Xinping
Title: Historical course of drug therapy for advanced or recurrent metastatic cervical cancer
Authors: Cao Xinping, Lv Xiaojuan, Sun Yat-sen University Cancer Hospital/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
Prof. Xiaojuan Lv
Deputy Director of the Department of Gynecologic Radiation Oncology, Zhejiang Provincial Cancer Hospital
Deputy Chief Physician, Doctor of Oncology, Master's Supervisor
Member of the Youth Council of the Chinese Anti-Cancer Association
Youth member of the Proximity Committee of the Chinese Anti-Cancer Association
Member of the Chinese Anti-Cancer Association Chinese and Western Integration of Cervical Cancer Special Committee
Member of the Special Committee for Integrated Screening of Cervical Cancer of the Chinese Anti-Cancer Association
Member of Gynecologic Oncology Branch of Zhejiang Medical Association
Secretary of the Gynecologic Oncology Branch of Zhejiang Rehabilitation Medical Association
The main treatment for advanced or recurrent metastatic cervical cancer is drug therapy, and some patients can be combined with local therapy, including surgery, radiotherapy, radiofrequency ablation and particle therapy. From the initial single-agent chemotherapy to the combination of chemotherapy, and then to targeted therapy and the current addition of immunotherapy, the drug treatment has undergone a huge historical evolution, and the treatment efficacy of patients has been gradually improved, and the survival time has also been significantly prolonged.
Single-agent chemotherapy: In the 80s of the last century, many researchers compared the efficacy and side effects of a variety of chemotherapy drugs in advanced recurrent and metastatic cervical cancer, and the American Gynecologic Oncology Group (GOG)64 study found that cisplatin monotherapy is the most effective drug for cervical cancer among all chemotherapy drugs, and its toxic side effects can be tolerated. This has established the important position of cisplatin in the drug treatment of cervical cancer, as shown in the table below.
Efficacy of single-agent chemotherapy in cervical cancer
Combination chemotherapy: due to the limited efficacy of cisplatin monotherapy, follow-up investigators gradually began to explore cisplatin-based combination drug therapy, including: cisplatin combined with paclitaxel, cisplatin combined with topotecan, cisplatin combined with ifosfamide, etc., among these combination regimens, GOG169 first confirmed that the combination of cisplatin combined with paclitaxel is superior to single-agent cisplatin, GOG204 further compared the efficacy differences between a variety of cisplatin-based combination regimens, and found that cisplatin combined with paclitaxel was better than cisplatin combined with topotecan, Cisplatin combined with gemcitabine and cisplatin combined with vinorelbine, these two clinical studies have established an important position in cisplatin combined with paclitaxel in advanced recurrent metastatic cervical cancer. In the era of chemotherapy, the first first-line chemotherapy regimen recommended by guidelines for advanced recurrent metastatic cervical cancer is cisplatin plus paclitaxel. But for cervical cancer patients who cannot tolerate cisplatin, which regimen should we choose, Japan's JGOG 0505 study conducted a non-inferior study of carboplatin combined with paclitaxel compared with cisplatin combined with paclitaxel, and found that the efficacy of carboplatin combined with paclitaxel is not inferior to that of cisplatin combined with paclitaxel, so the guidelines recommend that carboplatin can be considered instead for patients who cannot tolerate cisplatin.
Efficacy of combination chemotherapy in cervical cancer
Targeted therapy: The results of the 2009 GOG 227 study found that bevacizumab alone has a % efficacy rate in the second-line and late-line applications of advanced recurrent and metastatic cervical cancer, with a median progression-free survival (PFS) of 3.4 months and a median survival time (OS) of 7.3 months, and the 2015 NCCN guidelines recommend single-agent bevacizumab as a second-line drug for cervical cancer treatment. After bevacizumab achieved certain efficacy in the second-line application of cervical cancer, GOG240 was studied in first-line combination chemotherapy, and there were two chemotherapy regimens: cisplatin + paclitaxel and topotecan + paclitaxel, and the two chemotherapy regimens compared the efficacy and toxicity and side effects of bevacizumab with and without bevacizumab respectively, and found that the two chemotherapy regimens combined with bevacizumab significantly improved the OS and PFS of patients. This study established the position of bevacizumab in combination with chemotherapy drugs in the treatment of cervical cancer, and was soon recommended by the NCCN. In the era of targeted therapy, the combination of bevacizumab and TP/TC chemotherapy regimens is the first-line treatment of recurrent or metastatic cervical cancer, and single-agent bevacizumab is a second-line option.
A pivotal study of bevacizumab in cervical cancer
Immunotherapy: Immunotherapy is a great progress in the treatment of anti-tumor drugs in this century, most cervical cancers are HPV-related cervical cancers, which are immunothermal tumors, with the expression rate of PD-L1 as high as 70%-90%, and monotherapy immunotherapy has certain efficacy in the second-line and post-line applications of cervical cancer, with the effective rate of single-agent pam monotherapy in PD-L1-positive cervical cancer being 17%, and the effective rate of single-agent navuzumab being 26.3% Therefore, the NCCN guidelines first recommend the use of immunotherapy monotherapy in the second-line population of cervical cancer, but it requires a molecular target: PD-L1 positive, or MSI-H or TMB-H population. After achieving certain efficacy in the second-line application, immunotherapy further advanced to the first-line application, and KEYNOTE826 study compared the efficacy of paclitaxel + cisplatin/carboplatin± bevacizumab plus pembrolizumab and no pampumumab, and found that pampizumab combined with standard therapy significantly improved the objective response rate (ORR) of first-line cervical cancer: 65.9% vs 50.8%, and significantly improved overall OS: 18.0 months vs 10.4 months. Immediately recognized by experts, the NCCN guidelines added the recommended first-line drug treatment regimen for advanced recurrent and metastatic cervical cancer: paclitaxel + cisplatin/carboplatin± bevacizumab combined with pampizumab (for PD-L1-positive people). In addition, the domestic drugs selpalimab (PD-1 inhibitor) and cadonilimab (PD-1\CTLA-4 dual immune checkpoint inhibitor) have achieved good efficacy in the second-line single-immune application of cervical cancer, and have been approved for second-line application of cervical cancer.
ADC drugs: With the development of drug therapy, the research and application of antibody-drug conjugate (ADC) drugs have gradually emerged in advanced recurrent metastatic cervical cancer. ADC is a targeted anti-tumor drug that connects a biologically active small molecule drug to a monoclonal antibody through a chemical chain, and the monoclonal antibody acts as a carrier to target the small molecule drug into the target cell. The application of ADC drugs requires the presence of corresponding targets in the patient's body. At present, the drug approved by the FDA in the entry guidelines for cervical cancer is tisotumab vedotin (TV), an antibody-drug conjugate that targets tissue factors and carries tubulin inhibitors. In the InnovaTV 204 study, which included 101 patients with recurrent or metastatic cervical cancer who had received at least two prior therapies, the ORR of TV treatment was 24 percent and the disease control rate was 72 percent. In addition, research on TV combined with chemotherapy and TV combined with immunotherapy is also in full swing.
Historical course of drug therapy for cervical cancer: first-line medication
Current status of drug treatment: At present, the preferred recommended first-line drug treatment regimen for advanced recurrent metastatic cervical cancer is: TP/TC± bevacizumab + pampizumab (PD-L1 positive population), and the negative population is still TP/TC± bevacizumab. The preferred recommendations for second-line regimens are: pembrolizumab/savumumab (PD-L1-positive population), and other recommendations are: second-line chemotherapeutic agents, single-agent bevacizumab, and TV tissue factor. At present, there are many clinical studies to explore in the second-line application of advanced recurrent and metastatic cervical cancer: targeted drugs combined with immunodrugs, targeted drugs combined with second-line chemotherapy drugs, immunodrugs combined with second-line chemotherapy drugs, TV combined with immunization, TV combined with chemotherapy, etc., and more drug regimens for advanced recurrent and metastatic cervical cancer will be recommended in the guidelines in the future, further improving the efficacy of patients and prolonging the survival time of patients. New drugs continue to be developed and used in clinical practice, which has improved the survival time of patients with advanced or recurrent cervical cancer, and the toxic side effects have also been greatly reduced, which has brought good news to the majority of patients.
Pharmacological treatment of cervical cancer is recommended in the NCCN guidelines
CSCO Guidelines
Drafting/Reviewing:
Cao Xinping, Chairman of the Brachyradiotherapy Committee of the Chinese Anti-Cancer Association
Lv Xiaojuan, Youth Member of the Brachyradiotherapy Special Committee of the Chinese Anti-Cancer Association
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