Affiliated Cancer Hospital Makes a New Breakthrough in Precision Targeted Treatment of the “Most Aggressive Breast Cancer”
A randomized controlled umbrella phase II clinical study called "FUTURE-SUPER" for the first-line treatment of metastatic triple-negative breast cancer revealed that a new precision treatment based on the patient's molecular subtype and genomic markers, using chemotherapy combined with targeting or immunity, can significantly extend the progression-free survival of patients with metastatic triple-negative breast cancer, and the toxicity is controllable. This changes the clinical problem of single treatment method and poor efficacy in the past.
On the morning of January 9, 2024, the research results were published in the international oncology journal "The Lancet Oncology" in a fast-track manner. It is another landmark achievement of the integrated development of industry and medicine at Fudan University Shanghai Cancer Center. The research results were led by the clinical research team of Professor Shao Zhimin, Professor Wang Zhonghua, Professor Jiang Yizhou, and Professor Fan Lei of Fudan University Shanghai Cancer Center.
Conduct a series of prospective clinical studies based on the "Fudan Classification" of triple-negative breast cancer
Triple-negative breast cancer accounts for about 15% of the total number of breast cancers. It is known as the "most toxic breast cancer" because of its high malignancy, easy recurrence and metastasis, single treatment method, and lack of effective treatment targets. In 2019, Professors Shao Zhimin and Jiang Yizhou drew a genetic map based on the different molecular characteristics and treatment targets of the Chinese population, and drew the world's first "Fudan Classification" of triple-negative breast cancer, namely luminal androgen receptor type, immunomodulatory type, basal-like immunosuppressive type, and mesenchymal type (MES). This provides clinical and theoretical guidance for the precise treatment of triple-negative breast cancer.
Shao Zhimin, director of the breast surgery department and general surgery department of the hospital, said that in recent years, based on the "Fudan classification", our clinical research team has carried out a series of prospective clinical research projects called "FUTURE" in order to further verify the clinical value of the "Fudan classification" and explore potential treatment targets. Professor Jiang Yizhou, deputy director of the hospital, said that the "FUTURE" series of blockbuster research results based on the "Fudan Classification" have come out one after another. A study called "FUTURE-C-PLUS" achieved an objective response rate of up to 81.3% among first-line immunoregulatory patients. To this end, Professor Shao led the translational and clinical team to start a clinical trial called "FUTURE-SUPER" in 2020.
"FUTURE-SUPER" clinical trial releases latest blockbuster clinical research results
Professor Wang Zhonghua, deputy director of the hospital's Breast Surgery Department, said that this "FUTURE-SUPER" clinical trial project was jointly carried out by the hospital's Breast Surgery Department and Hengrui Pharmaceuticals. Clinical research teams do a good job in trial design and exploration of potential treatment targets. Pharmaceutical companies rely on drug research and development teams to continue to provide innovative drugs for the research platform. This is a useful exploration of the integration of medicine and industry.
After more than two years, the team completed the clinical trial and enrolled 139 patients. Patients enrolled were patients with metastatic triple-negative breast cancer or triple-negative breast cancer who were inoperable. The research team divided them into 5 treatment arms based on their subtypes and genomic biomarker test results, and randomly divided the enrolled patients into the "nab-paclitaxel" standard chemotherapy group and the precision treatment group that received traditional combination targeted or immune drugs.
The study showed that during a median follow-up period of 22.5 months, the median progression-free survival of patients in the precision therapy group was 11.3 months, which was 5.5 months longer than the 5.8 months in the traditional chemotherapy group. It should be pointed out that immunomodulatory patients are the group of patients with the largest increase in disease progression-free survival in the precision treatment program. Their median disease progression-free survival has reached 15.1 months, which is 8.6 months longer than traditional chemotherapy. This is currently the best survival benefit in the world.
Among them, a young triple-negative breast cancer patient was the biggest beneficiary of this study. In October 2019, she underwent modified radical surgery for right breast cancer in another hospital. The postoperative pathological diagnosis was triple-negative breast cancer, stage IIA. After surgery, she completed 8 courses of chemotherapy, with the last chemotherapy taking place in March 2020.
In April 2021, she was found to have bilateral lung and lymph node metastasis during follow-up. Lung biopsy pathology showed metastasis from breast cancer. After testing, it was found that it belonged to the immunomodulatory type (IM type) of the "Fudan Classification" of triple-negative breast cancer. The patient was enrolled in the FUTURE-SUPER study in April 2021, entered the precision treatment group, and received "nab-paclitaxel + camrelizumab + famitinib" treatment. After 10 courses of treatment, it was changed to camrelizumab + famitinib maintenance therapy. The tumor has now completely subsided, and the treatment time has been as long as 33 months. At present, the patient has returned to a high-quality life, and her work and life are back on track.
In addition, patients with basal-like immunosuppressive type and mesenchymal subtype survived 5.2 months longer than those with traditional chemotherapy after receiving precise treatment. "This result breaks the 'bottleneck' and limitations of targeted therapy in the treatment of triple-negative breast cancer." Professor Fan Lei from the Hospital's Breast Surgery Department said that the research results are very exciting. The objective response rate of the disease in the precision treatment group is as high as 80%, which is significantly higher than the 44.8% in the traditional chemotherapy group. The toxicity is controllable and there are no serious adverse reactions.
Medical enterprises cooperate, complement each other's advantages, and integrate industry and medicine to solve clinical problems
The results of this clinical research have important clinical significance. The results reveal that a combination of chemotherapy and immune-targeted precision treatment based on molecular subtypes and genomic markers has excellent efficacy and controllable safety for patients with triple-negative breast cancer. This will change the past situation where chemotherapy was the only treatment with poor efficacy.
Professor Shao Zhimin added that the successful implementation of the "FUTURE-SUPER" study has realized a new "closed-loop" innovative clinical research model of the entire chain from basic to clinical, medical-enterprise cooperation, complementary advantages, and integration of industry and medicine. It fully proves that the precise optimization of treatment plans for triple-negative breast cancer patients based on the "Fudan Classification" has important clinical significance.
"In order to further promote multi-center clinical trials of breast cancer precision treatment and accelerate the homogeneous development of breast cancer disciplines in China." Jiang Yizhou, deputy director of the hospital, introduced that the Breast Surgery Department of Fudan University Shanghai Cancer Center recently took the lead in establishing the Breast Cancer Precision Treatment Collaboration Group (BCTOP).
It is reported that the collaborative group relies on the Shanghai Cancer Prevention and Anti-Cancer Development Foundation and leverages the characteristics of the foundation to collaboratively carry out clinical research on precision treatment of breast cancer in multiple centers and build a translational research platform for breast cancer with Chinese characteristics. At the same time, based on the concept of precision medicine, it promotes the research and development of new drugs and new technologies. Each clinical center can improve its own scientific research system and improve the level of clinical and translational research by participating in the collaborative group's series of clinical studies.