-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
- Cosmetic Ingredient
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
China is a big country with a high incidence of esophageal cancer, and its mortality rate ranks fourth among malignant tumors
.
Neoadjuvant chemoradiation is the standard treatment for locally advanced resectable esophageal cancer, but the treatment failure rate is relatively high.
It is urgent to explore new treatment strategies
.
Recently, at the 24th National Conference on Clinical Oncology and the 2021 CSCO Annual Conference, a short-term neoadjuvant chemotherapy and radiotherapy combined with triprolimab neoadjuvant treatment of esophageal squamous cell carcinoma was co-chaired by Professor Zhu Xiangzhi and Professor Jiang Ming The Phase I clinical study-SCALE study was reported orally by CSCO
.
Here, Yimaitong invited two professors to interpret the SCALE research data and significance in depth, and talk freely about the application prospects of neoadjuvant radiotherapy and chemotherapy combined with immunotherapy in locally advanced esophageal cancer
.
Expert Profile Professor Zhu Xiangzhi, Chief Physician, Department of Radiotherapy, Jiangsu Cancer Hospital, Master's Supervisor, Nanjing Medical University, Member of the Chinese Society of Clinical Oncology (CSCO) Esophageal Cancer Expert Committee, Member of the Lung Cancer Group of the Chinese Anti-Cancer Association Cancer Radiotherapy Professional Committee, published more than 10 articles and participated in the editor Participated in the translation of 6 monographs.
Professor Ming Jiang has worked in the Department of Thoracic Surgery of Jiangsu Cancer Hospital for more than 20 years.
He is good at the treatment of esophageal cancer, lung cancer, and mediastinal tumors.
Invasive technique, has unique experience in perioperative management and incision pain
.
After returning from studying abroad, he introduced advanced foreign treatment concepts and advocated comprehensive preoperative treatment of esophageal cancer and right thoracotomy, two-field and three-field lymphadenectomy, which greatly improved the treatment effect and postoperative quality of life
.
Currently focusing on the diagnosis and treatment of small lung nodules and comprehensive treatment of esophageal cancer, including thoracoscopic minimally invasive surgery, preoperative neoadjuvant radiochemical immunotherapy + surgery, rescue surgery after radiotherapy failure, etc.
, which greatly improves the treatment effect and ranks domestically.
Leading position, especially in the preoperative neoadjuvant treatment of operable esophageal cancer, and has achieved satisfactory results in terms of treatment safety, control of side effects, and long-term survival rate of surgical efficacy
.
Yimaitong: Could the two professors talk about the current status and bottlenecks of neoadjuvant therapy for locally advanced resectable esophageal cancer? And the design highlights of SCALE research? Professor Ming Jiang: In recent years, the concept of neoadjuvant therapy has gradually become popular for patients with locally advanced resectable esophageal cancer
.
However, the current domestic neoadjuvant treatment programs are mainly neoadjuvant chemotherapy, and the curative effect is not very satisfactory
.
Recently, with the introduction of immunotherapy, neoadjuvant chemotherapy combined with immunotherapy programs have been increasingly used clinically, but some patients still have poor efficacy
.
In clinical practice, if neoadjuvant treatment fails to control the disease in time, once the disease progresses, the patient may lose the opportunity for surgery or bring great difficulties and risks to the operation, especially in the trachea, bronchus, or aortic arch.
Tumors near the organs
.
Based on this, in order to improve the neoadjuvant treatment of locally advanced resectable esophageal cancer, the SCALE study came into being
.
The study explored the efficacy and safety of neoadjuvant chemoradiation + immunotherapy triple therapy, and innovatively adopted a short-term radiotherapy program
.
Professor Zhu Xiangzhi: At the beginning of the SCALE study design, we considered the efficacy and safety of adding immunotherapy to standard neoadjuvant radiotherapy and chemotherapy
.
In theory, the lethality of triple therapy on tumors is greater than neoadjuvant radiotherapy and chemotherapy, but in addition to the efficacy, clinical considerations should also be given to whether patients can tolerate triple neoadjuvant therapy
.
Therefore, the intensity of radiotherapy was adjusted in the SCALE study design.
On the one hand, it is to reduce unnecessary severe toxicity.
On the other hand, it is hoped that by shortening the course of radiotherapy and increasing the divided dose, radiotherapy and immunotherapy can achieve better synergy.
This is also the first short-term neoadjuvant study related to esophageal cancer at home and abroad
.
Therefore, in the selection of immunological drugs, the safer triprolizumab was finally selected
.
The drug is the first domestically-made PD-1 immunotherapy drug to be marketed in China.
It has been approved for the treatment of melanoma, nasopharyngeal carcinoma, and urothelial cancer.
This year, it has also obtained Phase III clinical confirmation in the first-line treatment of advanced esophageal cancer.
Sexual data
.
Yimaitong: Could the two professors introduce the preliminary results of the SCALE study? And the transformational relationship between pCR rate and long-term survival? Professor Ming Jiang: The preliminary results of the SCALE study show that the neoadjuvant triple therapy has high local tumor control rate, tolerable safety, and greatly improves the complete resection rate
.
For the aforementioned tumors close to important organs, triple therapy can effectively circumvent the risk of disease progression caused by conventional neoadjuvant treatments, so that the disease is downgraded and the patient has the opportunity for surgery
.
Professor Zhu Xiangzhi: In previous studies of neoadjuvant therapy for esophageal cancer, such as the 5010 and CROSS studies, the pathological complete remission (pCR) rate is a very important observation index for efficacy
.
In the SCALE study, the pCR rate of primary tumors was 53.
8%, and the overall pCR rate of primary tumors and lymph nodes was 46.
2%
.
In clinical studies in medicine, recognized as the best indicators of efficacy is overall survival (OS) rate, including other disease-free survival (DFS) rate, the effective rate, pCR rate
.
A large number of previous studies have shown that the pCR rate of neoadjuvant therapy has a strong correlation with long-term survival
.
Therefore, this study used the pCR rate as a surrogate indicator to predict long-term prognostic survival through short-term treatment response
.
Of course, in the age of immunotherapy, whether short-term index benefits can translate into OS requires longer follow-up and observation
.
In addition, the higher the pCR rate is not the higher, but the more accurate the better
.
Therefore, pathological quality control is very important for neoadjuvant therapy research
.
In the SCALE study, we conducted pathological-related explorations, and detailed data will be reported in the follow-up
.
Yimaitong: Based on the results of the SCALE study, what is your opinion on the setting of operation time and how to avoid the risk of perioperative treatment? Professor Ming Jiang: Surgery for esophageal cancer is a major operation.
It has certain requirements for the patient's preoperative physique.
Good physique surgery is relatively safer
.
Usually, most patients with esophageal cancer have some obvious symptoms or malnutrition at the time of treatment
.
After receiving triple neoadjuvant therapy, some patients will resume eating and their physical fitness will be significantly improved
.
Of course, patients will also experience treatment-related toxicity, and it will take a certain time for the toxicity to ease or disappear
.
In the early stage, the SCALE study used six weeks as the rest time for patients after neoadjuvant therapy.
However, as the study progressed, we found that patients generally recovered only after five or six weeks.
Therefore, the study further extended the operation time to eight weeks
.
After six to eight weeks of recovery, the patient’s nutritional status is improved, and the physique is improved compared to when he first visited the doctor, which improves the safety of the operation from the source
.
In addition, neoadjuvant therapy has also controlled the lesions well, ensuring safety as a whole
.
In the SCALE study, after triple neoadjuvant therapy, some patients will experience transient hypotension during and after surgery.
By actively supplementing volume and colloids, adding vasoactive drugs, and diuresis, it can be well avoided The perioperative risk ensures that the patient is discharged from the hospital smoothly
.
Most of the patients received triple neoadjuvant therapy and the lesions retreated significantly, which is beneficial to reduce the difficulty of the operation; a small number of patients may have an immune response, leading to adhesion of the lesion and surrounding organs, which poses certain challenges to the operation
.
But overall, the feasibility of surgery after triple neoadjuvant therapy is slightly higher than that of patients who have not undergone neoadjuvant therapy
.
Yimaitong: Will immunotherapy and radiotherapy increase the risk of patients with related pneumonia? Professor Zhu Xiangzhi: Whether radiotherapy combined with immunotherapy will increase the risk of radiation pneumonia or immune pneumonia is still inconclusive
.
In the KEYNOTE-799 study, after receiving concurrent radiotherapy and chemotherapy combined with immunotherapy, a small number of patients with locally advanced lung cancer died due to pulmonary toxicity
.
However, clinical practice experience shows that under the same dose of radiation, the probability of pneumonia in esophageal cancer and lung cancer is different, and the probability of the latter is higher
.
In order to avoid the occurrence of adverse reactions such as pneumonia, the SCALE study took a series of measures: first, the study reduced the total dose of radiotherapy; second, reformed and innovated the delineation of the radiotherapy target area, and introduced the combined target area of radiotherapy and thoracic surgery.
Concept; Third, ono irradiation is used for tumor and lymph node radiotherapy to reduce the impact on the patient’s lungs
.
In the end, the results of the SCALE study showed that none of the 18 patients developed radiation pneumonia or immune pneumonia
.
Yimaitong: In the age of immunotherapy, what changes and challenges will the standard plan of neoadjuvant treatment for locally advanced resectable esophageal cancer be in the future? Prof.
Ming Jiang: In recent years, the addition of immunotherapy has made neoadjuvant therapy more effective, which has brought some challenges and opportunities to surgeons
.
In the eyes of surgeons, in addition to the primary focus and visible lymph nodes of esophageal cancer, occult lesions are actually the key factors affecting the efficacy
.
The early three-field lymphatic dissection hopes to expand the scope of surgical resection to remove concealed lesions, but this surgical method is very traumatic and is not well accepted by patients
.
With the continuous progress of neoadjuvant therapy, it is clinically expected to kill occult lesions in the neoadjuvant therapy stage
.
In the future, surgery for esophageal cancer may only require removal of the primary tumor and visible lymph nodes, further reducing the scope of surgery
.
Professor Zhu Xiangzhi: Both clinical research data and practical experience show that immunotherapy and radiotherapy have a strong synergistic effect, but its mechanism of action and the best combination plan need to be explored and clarified
.
In the age of immunotherapy, how to better coordinate radiotherapy and immunity? The SCALE study tried a combination of 2.
5Gy×12 short-course radiotherapy, immunotherapy and chemotherapy.
The preliminary results are encouraging, but the best segmentation plan needs further progress.
Clinical research
.
The sooner the immunotherapy is used, the greater the benefit to the patient, but the advancement of immunotherapy not only pays attention to the tumor regression, but also controls the toxicity to ensure the smooth progress of the operation
.
In the long run, triple neoadjuvant therapy is a very promising development direction, but more studies with large and medium sample sizes are needed for further verification
.
About Toripalimab Injection (Toripalimab Injection).
Toripalimab Injection (trade name: Toripalimab Injection, English name: Toripalimab Injection) is the first domestically produced PD-1 target approved for marketing in China.
Monoclonal antibody drugs have been supported by major national science and technology projects
.
This product is currently approved by NMPA.
Indications include: for the treatment of unresectable or metastatic melanoma patients who have previously received systemic treatment failure; for patients with recurrent/metastatic nasopharyngeal carcinoma who have previously received second-line and above systemic treatment failures For the treatment of locally advanced or metastatic urothelial cancer that has failed platinum-containing chemotherapy, including neoadjuvant or adjuvant chemotherapy, which has progressed within 12 months
.
In addition, Teriplizumab has also obtained the "Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Melanoma", "CSCO Guidelines for the Diagnosis and Treatment of Head and Neck Tumors", "CSCO Guidelines for the Diagnosis and Treatment of Nasopharyngeal Carcinoma", and "CSCO Urothelial Carcinoma Recommendations of "Guidelines for Diagnosis and Treatment" and "Guidelines for Clinical Application of CSCO Immune Checkpoint Inhibitors"
.
.
Neoadjuvant chemoradiation is the standard treatment for locally advanced resectable esophageal cancer, but the treatment failure rate is relatively high.
It is urgent to explore new treatment strategies
.
Recently, at the 24th National Conference on Clinical Oncology and the 2021 CSCO Annual Conference, a short-term neoadjuvant chemotherapy and radiotherapy combined with triprolimab neoadjuvant treatment of esophageal squamous cell carcinoma was co-chaired by Professor Zhu Xiangzhi and Professor Jiang Ming The Phase I clinical study-SCALE study was reported orally by CSCO
.
Here, Yimaitong invited two professors to interpret the SCALE research data and significance in depth, and talk freely about the application prospects of neoadjuvant radiotherapy and chemotherapy combined with immunotherapy in locally advanced esophageal cancer
.
Expert Profile Professor Zhu Xiangzhi, Chief Physician, Department of Radiotherapy, Jiangsu Cancer Hospital, Master's Supervisor, Nanjing Medical University, Member of the Chinese Society of Clinical Oncology (CSCO) Esophageal Cancer Expert Committee, Member of the Lung Cancer Group of the Chinese Anti-Cancer Association Cancer Radiotherapy Professional Committee, published more than 10 articles and participated in the editor Participated in the translation of 6 monographs.
Professor Ming Jiang has worked in the Department of Thoracic Surgery of Jiangsu Cancer Hospital for more than 20 years.
He is good at the treatment of esophageal cancer, lung cancer, and mediastinal tumors.
Invasive technique, has unique experience in perioperative management and incision pain
.
After returning from studying abroad, he introduced advanced foreign treatment concepts and advocated comprehensive preoperative treatment of esophageal cancer and right thoracotomy, two-field and three-field lymphadenectomy, which greatly improved the treatment effect and postoperative quality of life
.
Currently focusing on the diagnosis and treatment of small lung nodules and comprehensive treatment of esophageal cancer, including thoracoscopic minimally invasive surgery, preoperative neoadjuvant radiochemical immunotherapy + surgery, rescue surgery after radiotherapy failure, etc.
, which greatly improves the treatment effect and ranks domestically.
Leading position, especially in the preoperative neoadjuvant treatment of operable esophageal cancer, and has achieved satisfactory results in terms of treatment safety, control of side effects, and long-term survival rate of surgical efficacy
.
Yimaitong: Could the two professors talk about the current status and bottlenecks of neoadjuvant therapy for locally advanced resectable esophageal cancer? And the design highlights of SCALE research? Professor Ming Jiang: In recent years, the concept of neoadjuvant therapy has gradually become popular for patients with locally advanced resectable esophageal cancer
.
However, the current domestic neoadjuvant treatment programs are mainly neoadjuvant chemotherapy, and the curative effect is not very satisfactory
.
Recently, with the introduction of immunotherapy, neoadjuvant chemotherapy combined with immunotherapy programs have been increasingly used clinically, but some patients still have poor efficacy
.
In clinical practice, if neoadjuvant treatment fails to control the disease in time, once the disease progresses, the patient may lose the opportunity for surgery or bring great difficulties and risks to the operation, especially in the trachea, bronchus, or aortic arch.
Tumors near the organs
.
Based on this, in order to improve the neoadjuvant treatment of locally advanced resectable esophageal cancer, the SCALE study came into being
.
The study explored the efficacy and safety of neoadjuvant chemoradiation + immunotherapy triple therapy, and innovatively adopted a short-term radiotherapy program
.
Professor Zhu Xiangzhi: At the beginning of the SCALE study design, we considered the efficacy and safety of adding immunotherapy to standard neoadjuvant radiotherapy and chemotherapy
.
In theory, the lethality of triple therapy on tumors is greater than neoadjuvant radiotherapy and chemotherapy, but in addition to the efficacy, clinical considerations should also be given to whether patients can tolerate triple neoadjuvant therapy
.
Therefore, the intensity of radiotherapy was adjusted in the SCALE study design.
On the one hand, it is to reduce unnecessary severe toxicity.
On the other hand, it is hoped that by shortening the course of radiotherapy and increasing the divided dose, radiotherapy and immunotherapy can achieve better synergy.
This is also the first short-term neoadjuvant study related to esophageal cancer at home and abroad
.
Therefore, in the selection of immunological drugs, the safer triprolizumab was finally selected
.
The drug is the first domestically-made PD-1 immunotherapy drug to be marketed in China.
It has been approved for the treatment of melanoma, nasopharyngeal carcinoma, and urothelial cancer.
This year, it has also obtained Phase III clinical confirmation in the first-line treatment of advanced esophageal cancer.
Sexual data
.
Yimaitong: Could the two professors introduce the preliminary results of the SCALE study? And the transformational relationship between pCR rate and long-term survival? Professor Ming Jiang: The preliminary results of the SCALE study show that the neoadjuvant triple therapy has high local tumor control rate, tolerable safety, and greatly improves the complete resection rate
.
For the aforementioned tumors close to important organs, triple therapy can effectively circumvent the risk of disease progression caused by conventional neoadjuvant treatments, so that the disease is downgraded and the patient has the opportunity for surgery
.
Professor Zhu Xiangzhi: In previous studies of neoadjuvant therapy for esophageal cancer, such as the 5010 and CROSS studies, the pathological complete remission (pCR) rate is a very important observation index for efficacy
.
In the SCALE study, the pCR rate of primary tumors was 53.
8%, and the overall pCR rate of primary tumors and lymph nodes was 46.
2%
.
In clinical studies in medicine, recognized as the best indicators of efficacy is overall survival (OS) rate, including other disease-free survival (DFS) rate, the effective rate, pCR rate
.
A large number of previous studies have shown that the pCR rate of neoadjuvant therapy has a strong correlation with long-term survival
.
Therefore, this study used the pCR rate as a surrogate indicator to predict long-term prognostic survival through short-term treatment response
.
Of course, in the age of immunotherapy, whether short-term index benefits can translate into OS requires longer follow-up and observation
.
In addition, the higher the pCR rate is not the higher, but the more accurate the better
.
Therefore, pathological quality control is very important for neoadjuvant therapy research
.
In the SCALE study, we conducted pathological-related explorations, and detailed data will be reported in the follow-up
.
Yimaitong: Based on the results of the SCALE study, what is your opinion on the setting of operation time and how to avoid the risk of perioperative treatment? Professor Ming Jiang: Surgery for esophageal cancer is a major operation.
It has certain requirements for the patient's preoperative physique.
Good physique surgery is relatively safer
.
Usually, most patients with esophageal cancer have some obvious symptoms or malnutrition at the time of treatment
.
After receiving triple neoadjuvant therapy, some patients will resume eating and their physical fitness will be significantly improved
.
Of course, patients will also experience treatment-related toxicity, and it will take a certain time for the toxicity to ease or disappear
.
In the early stage, the SCALE study used six weeks as the rest time for patients after neoadjuvant therapy.
However, as the study progressed, we found that patients generally recovered only after five or six weeks.
Therefore, the study further extended the operation time to eight weeks
.
After six to eight weeks of recovery, the patient’s nutritional status is improved, and the physique is improved compared to when he first visited the doctor, which improves the safety of the operation from the source
.
In addition, neoadjuvant therapy has also controlled the lesions well, ensuring safety as a whole
.
In the SCALE study, after triple neoadjuvant therapy, some patients will experience transient hypotension during and after surgery.
By actively supplementing volume and colloids, adding vasoactive drugs, and diuresis, it can be well avoided The perioperative risk ensures that the patient is discharged from the hospital smoothly
.
Most of the patients received triple neoadjuvant therapy and the lesions retreated significantly, which is beneficial to reduce the difficulty of the operation; a small number of patients may have an immune response, leading to adhesion of the lesion and surrounding organs, which poses certain challenges to the operation
.
But overall, the feasibility of surgery after triple neoadjuvant therapy is slightly higher than that of patients who have not undergone neoadjuvant therapy
.
Yimaitong: Will immunotherapy and radiotherapy increase the risk of patients with related pneumonia? Professor Zhu Xiangzhi: Whether radiotherapy combined with immunotherapy will increase the risk of radiation pneumonia or immune pneumonia is still inconclusive
.
In the KEYNOTE-799 study, after receiving concurrent radiotherapy and chemotherapy combined with immunotherapy, a small number of patients with locally advanced lung cancer died due to pulmonary toxicity
.
However, clinical practice experience shows that under the same dose of radiation, the probability of pneumonia in esophageal cancer and lung cancer is different, and the probability of the latter is higher
.
In order to avoid the occurrence of adverse reactions such as pneumonia, the SCALE study took a series of measures: first, the study reduced the total dose of radiotherapy; second, reformed and innovated the delineation of the radiotherapy target area, and introduced the combined target area of radiotherapy and thoracic surgery.
Concept; Third, ono irradiation is used for tumor and lymph node radiotherapy to reduce the impact on the patient’s lungs
.
In the end, the results of the SCALE study showed that none of the 18 patients developed radiation pneumonia or immune pneumonia
.
Yimaitong: In the age of immunotherapy, what changes and challenges will the standard plan of neoadjuvant treatment for locally advanced resectable esophageal cancer be in the future? Prof.
Ming Jiang: In recent years, the addition of immunotherapy has made neoadjuvant therapy more effective, which has brought some challenges and opportunities to surgeons
.
In the eyes of surgeons, in addition to the primary focus and visible lymph nodes of esophageal cancer, occult lesions are actually the key factors affecting the efficacy
.
The early three-field lymphatic dissection hopes to expand the scope of surgical resection to remove concealed lesions, but this surgical method is very traumatic and is not well accepted by patients
.
With the continuous progress of neoadjuvant therapy, it is clinically expected to kill occult lesions in the neoadjuvant therapy stage
.
In the future, surgery for esophageal cancer may only require removal of the primary tumor and visible lymph nodes, further reducing the scope of surgery
.
Professor Zhu Xiangzhi: Both clinical research data and practical experience show that immunotherapy and radiotherapy have a strong synergistic effect, but its mechanism of action and the best combination plan need to be explored and clarified
.
In the age of immunotherapy, how to better coordinate radiotherapy and immunity? The SCALE study tried a combination of 2.
5Gy×12 short-course radiotherapy, immunotherapy and chemotherapy.
The preliminary results are encouraging, but the best segmentation plan needs further progress.
Clinical research
.
The sooner the immunotherapy is used, the greater the benefit to the patient, but the advancement of immunotherapy not only pays attention to the tumor regression, but also controls the toxicity to ensure the smooth progress of the operation
.
In the long run, triple neoadjuvant therapy is a very promising development direction, but more studies with large and medium sample sizes are needed for further verification
.
About Toripalimab Injection (Toripalimab Injection).
Toripalimab Injection (trade name: Toripalimab Injection, English name: Toripalimab Injection) is the first domestically produced PD-1 target approved for marketing in China.
Monoclonal antibody drugs have been supported by major national science and technology projects
.
This product is currently approved by NMPA.
Indications include: for the treatment of unresectable or metastatic melanoma patients who have previously received systemic treatment failure; for patients with recurrent/metastatic nasopharyngeal carcinoma who have previously received second-line and above systemic treatment failures For the treatment of locally advanced or metastatic urothelial cancer that has failed platinum-containing chemotherapy, including neoadjuvant or adjuvant chemotherapy, which has progressed within 12 months
.
In addition, Teriplizumab has also obtained the "Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Melanoma", "CSCO Guidelines for the Diagnosis and Treatment of Head and Neck Tumors", "CSCO Guidelines for the Diagnosis and Treatment of Nasopharyngeal Carcinoma", and "CSCO Urothelial Carcinoma Recommendations of "Guidelines for Diagnosis and Treatment" and "Guidelines for Clinical Application of CSCO Immune Checkpoint Inhibitors"
.
