-
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
*Only for medical professionals to read and reference Nivolumab brings innovative options for upper gastrointestinal cancer treatment
.
After nearly ten years, gastric cancer treatment finally ushered in changes in 2021.
At the end of August, nivolumab combined with chemotherapy was approved for the first-line treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma, becoming China The first and currently the only immunocombination therapy approved for the first-line treatment of advanced gastric cancer, and is not limited by the expression level of PD-L1
.
In the entire population, this is a major breakthrough in the first-line treatment of gastric cancer after the chemotherapy era
.
Also undergoing treatment changes is the field of esophageal cancer.
The three studies of CheckMate-649/648/577 can be said to "enclose" the front-line treatment of squamous cell carcinoma and adenocarcinoma in the field of esophagus.
To survive, there are more means
.
What is the significance of the approval of the first-line indication of nivolumab for the treatment of gastric cancer for the treatment of gastric cancer in China? What are the characteristics of CheckMate-649 research that won the 2021 CSCO Outstanding Paper Award? In addition to gastric cancer, what are the latest research advances in China's high-incidence upper gastrointestinal cancers? Just as the ESMO and CSCO annual meeting had just passed, Professor Zhang Xiaotian, chief physician of the Department of Digestive Oncology, Peking University Cancer Hospital, was invited to give an in-depth explanation on the latest data of the CheckMate series of studies on the upper gastrointestinal tract
.
Professor Zhang Xiaotian’s wonderful video has been a bottleneck for ten years.
Compared with the continuous breakthroughs in innovative treatments of other cancer types, Nivolumab finally broke
.
It can be said that advanced gastric cancer has made little progress .
"The heterogeneity of gastric cancer is very strong, and it is difficult for clinical studies to produce prolonged survival results in the entire population
.
If a relatively limited population is screened out, the theoretical possibility of benefit is greater, but this will lead to longer population enrollment time and more challenging research design
.
Professor Zhang Xiaotian explained the reason why the first-line treatment of gastric cancer has not achieved breakthroughs for many years
.
Fortunately, after many tests, the success of immunotherapy has successively broken the dual dilemma of “drug shortage” and “first-line bottleneck” in the treatment of advanced gastric cancer.
The patient brings hope of long-term survival
.
"The indication of nivolumab combined with chemotherapy in the first-line treatment of advanced gastric cancer is approved for the whole population, which is a very progressive challenge for doctors, patients and regulatory authorities
.
"Professor Zhang Xiaotian pointed out that on the one hand, the indications cover all first-line patients with advanced gastric cancer, whether the application of the whole population in the real world can achieve more significant survival benefits for patients with PD-L1 CPS ≥ 5 in clinical trials.
It is an issue worthy of attention and follow-up; on the other hand, the era of immunotherapy has refreshed doctors’ understanding of tumor treatment, from a single cancer target, to the surface of tumor cells and lymphocytes, to the nutritional status, immune status, and The overall situation of immune function and so on
.
Through this transformation, doctors can also gradually learn and understand the characteristics of immuno-oncology treatment more deeply
.
More importantly, immunocombination therapy provides a very beneficial weapon for the first-line treatment of advanced gastric cancer
.
Nowadays After the indication is approved, it will be possible to be included in medical insurance in the future and benefit more patients
.
To
solve the urgent need, the Chinese subgroup will benefit even more.
"This combination of immunization and chemotherapy for advanced gastric cancer first-line indications for the entire population is approved in China , Based on Chinese practice
.
Compared with the US FDA approval, it is more confident that the Chinese subgroup data is indeed better than the global data, whether it is the whole population, or CPS≥1 or CPS≥5
.
"Professor Zhang Xiaotian commented
.
Focusing on the results of the experimental group (nivolumab combined chemotherapy group) of the CheckMate-649 study on which the approval was based: the median OS and PFS of all randomized populations worldwide were 13.
8 and 7.
7 months, respectively [1 ]
.
All randomized data Chinese population subgroups showed a median OS of 14.
3 months, about 39% lower risk of death, median PFS was 8.
3 months, reduce the risk of recurrence and mortality of about 43% [2]; wherein PD- The OS and PFS of patients with L1 CPS ≥ 5 can reach 15.
5 and 8.
5 months
.
In the
Chinese subgroup, the objective response rate (ORR) of the nivolumab combined chemotherapy group reached 59% [4], compared with the traditional chemotherapy era The ORR of 35%-45% increased by nearly 20%; and the duration of remission (DoR) reached more than 12 months
.
“This shows that patients with advanced gastric cancer can get tumor regression with a high probability through first-line immunotherapy, and they can get a long time.
Disease control, and the quality of life of patients during this period of time is also very good
.
"Professor Zhang Xiaotian added analysis
.
At the
safety level, no new safety signals were observed in the CheckMate-649 study, and the incidence of treatment-related adverse events (TRAEs) in some patients with PD-L1 CPS≥5 is similar to that of all patients
.
For China The more important information for patients is that among all patients in the Chinese subgroup who received nivolumab combined with chemotherapy, no one died due to treatment-related adverse reactions
.
Ingenious design, the overall survival benefit fully covers CheckMate- The 649 study adopted a clever design
.
Although OS was used as a secondary endpoint in the study, the alpha value was also assigned at the beginning of the study, so that the difference achieved for each endpoint was statistically significant
.
Thanks to this, the first-line treatment indications approved for this immunotherapy combination in the United States and China eventually covered all patients with advanced gastric cancer
.
"The basic premise that China and the United States can approve the indication for the whole population is the same: the OS benefit of the whole population is not the concomitant event observed after all the alpha values are assigned to the primary research endpoint.
This is a reasonable requirement in statistical principles.
.
"but Professor Zhang Xiaotian analysis:" give the whole crowd indications, focusing on the United States and China considerations there may be different, better performance of Chinese subgroup data should also consider the Chinese regulatory authorities
.
"" because the Chinese gastric cancer The onset of disease is characterized by late discovery, late staging, large tumor burden at the time of diagnosis, and relatively poor physical status.
Such patients need to reduce tumor burden as soon as possible
.
From this perspective, for the entire clinical practice in China, this is recommended for the entire population A treatment with relatively strong curative effect does have its reason
.
"Multiple breakthroughs benefit the upper gastrointestinal tract More treatments In addition to gastric cancer, in recent years, nivolumab-based therapies have also continuously made breakthroughs in the research of high-incidence esophageal cancer in China.
.
For example, the CheckMate-648 study showed that nivolumab + chemotherapy, nivolumumab + ipilimumab for first-line treatment of advanced esophageal squamous cell carcinoma, compared with standard chemotherapy, can achieve significant OS benefits, and regardless of the patient's PD-L1 Expression level (for specific research data, please refer to → 2021 ASCO Annual Meeting Report LBA Research CheckMate-648)
.
"China's esophageal cancer is quite different from global esophageal cancer.
Squamous cell carcinoma is the majority.
The CheckMate-648 study mainly included patients with esophageal squamous cell carcinoma.
This is a very important reference for the treatment of esophageal squamous cell carcinoma in China, " said Professor Zhang Xiaotian
.
.
Based on the research results of CheckMate-649 and CheckMate-648, nivolumab became the first and currently the only first-line confirmed treatment for various histological types (squamous cell carcinoma, adenocarcinoma) and tumor sites (stomach, esophagus, gastroesophageal junction) ) Of upper gastrointestinal tumors, all PD-1/PD-L1 inhibitors with significant OS benefit
.
In addition, the CheckMate-577 study provides new ideas for postoperative adjuvant treatment of patients with esophageal cancer
.
Studies have shown that nivolumab adjuvant treatment of esophageal cancer and gastroesophageal junction cancer after neoadjuvant concurrent chemoradiation and surgery can double the disease-free survival (DFS) of patients compared with placebo
.
Based on the results of CheckMate-577, nivolumab has been approved by the U.
S.
Food and Drug Administration (FDA) in May 2021, becoming the world's first immunotherapy for adjuvant treatment of esophageal cancer
.
From the late stage to the first-line stage, to adjuvant treatment during the perioperative period, with the accumulation of more research data, nivolumab-based immunotherapy will benefit more patients with upper gastrointestinal tumors
.
Expert profile Professor Zhang Xiaotian, Peking University Cancer Hospital, Peking University Cancer Hospital, Deputy Director of International Cooperation and Exchange Department, Executive Deputy Director of Internal Medicine Teaching and Research Office Doctor of Medicine, Chief Physician, Associate Professor, Master Tutor, Chinese Society of Clinical Oncology Youth Expert Committee Chairman, China Member of the Executive Committee of the Clinical Oncology Society Member of the Gastric Cancer Professional Committee of the Chinese Anti-Cancer Association Member of the Evidence-Based Medicine Group of the Sixth Committee of Epidemiology Branch: Reviewer of "Journal of Clinical Oncology", "Chinese Journal of Oncology", "Chinese Medical Journal", and editorial board member of "Chinese Journal of Clinical Nutrition" and "Chinese Medical Journal of Chinese People's Liberation Army"; Responsible for more than ten phase II and phase III international multi-center clinical studies and a number of domestic phase II and phase III clinical studies; published more than ten SCI articles and dozens of core journals; participated in the compilation of the monograph "Advanced Oncology Course", etc.
.
References[1]Janjigian YY, Shitara K, Moehler M, et al.
First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial[J].
The Lancet, 2021, 398(10294): 27-40.
[2]Shen, L.
et.
al.
2021, First-line nivolumab plus chemotherapy versus chemotherapy in patients with advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis, AACR 2021, presentation number CT184, April 2021.
*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform
.
After nearly ten years, gastric cancer treatment finally ushered in changes in 2021.
At the end of August, nivolumab combined with chemotherapy was approved for the first-line treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma, becoming China The first and currently the only immunocombination therapy approved for the first-line treatment of advanced gastric cancer, and is not limited by the expression level of PD-L1
.
In the entire population, this is a major breakthrough in the first-line treatment of gastric cancer after the chemotherapy era
.
Also undergoing treatment changes is the field of esophageal cancer.
The three studies of CheckMate-649/648/577 can be said to "enclose" the front-line treatment of squamous cell carcinoma and adenocarcinoma in the field of esophagus.
To survive, there are more means
.
What is the significance of the approval of the first-line indication of nivolumab for the treatment of gastric cancer for the treatment of gastric cancer in China? What are the characteristics of CheckMate-649 research that won the 2021 CSCO Outstanding Paper Award? In addition to gastric cancer, what are the latest research advances in China's high-incidence upper gastrointestinal cancers? Just as the ESMO and CSCO annual meeting had just passed, Professor Zhang Xiaotian, chief physician of the Department of Digestive Oncology, Peking University Cancer Hospital, was invited to give an in-depth explanation on the latest data of the CheckMate series of studies on the upper gastrointestinal tract
.
Professor Zhang Xiaotian’s wonderful video has been a bottleneck for ten years.
Compared with the continuous breakthroughs in innovative treatments of other cancer types, Nivolumab finally broke
.
It can be said that advanced gastric cancer has made little progress .
"The heterogeneity of gastric cancer is very strong, and it is difficult for clinical studies to produce prolonged survival results in the entire population
.
If a relatively limited population is screened out, the theoretical possibility of benefit is greater, but this will lead to longer population enrollment time and more challenging research design
.
Professor Zhang Xiaotian explained the reason why the first-line treatment of gastric cancer has not achieved breakthroughs for many years
.
Fortunately, after many tests, the success of immunotherapy has successively broken the dual dilemma of “drug shortage” and “first-line bottleneck” in the treatment of advanced gastric cancer.
The patient brings hope of long-term survival
.
"The indication of nivolumab combined with chemotherapy in the first-line treatment of advanced gastric cancer is approved for the whole population, which is a very progressive challenge for doctors, patients and regulatory authorities
.
"Professor Zhang Xiaotian pointed out that on the one hand, the indications cover all first-line patients with advanced gastric cancer, whether the application of the whole population in the real world can achieve more significant survival benefits for patients with PD-L1 CPS ≥ 5 in clinical trials.
It is an issue worthy of attention and follow-up; on the other hand, the era of immunotherapy has refreshed doctors’ understanding of tumor treatment, from a single cancer target, to the surface of tumor cells and lymphocytes, to the nutritional status, immune status, and The overall situation of immune function and so on
.
Through this transformation, doctors can also gradually learn and understand the characteristics of immuno-oncology treatment more deeply
.
More importantly, immunocombination therapy provides a very beneficial weapon for the first-line treatment of advanced gastric cancer
.
Nowadays After the indication is approved, it will be possible to be included in medical insurance in the future and benefit more patients
.
To
solve the urgent need, the Chinese subgroup will benefit even more.
"This combination of immunization and chemotherapy for advanced gastric cancer first-line indications for the entire population is approved in China , Based on Chinese practice
.
Compared with the US FDA approval, it is more confident that the Chinese subgroup data is indeed better than the global data, whether it is the whole population, or CPS≥1 or CPS≥5
.
"Professor Zhang Xiaotian commented
.
Focusing on the results of the experimental group (nivolumab combined chemotherapy group) of the CheckMate-649 study on which the approval was based: the median OS and PFS of all randomized populations worldwide were 13.
8 and 7.
7 months, respectively [1 ]
.
All randomized data Chinese population subgroups showed a median OS of 14.
3 months, about 39% lower risk of death, median PFS was 8.
3 months, reduce the risk of recurrence and mortality of about 43% [2]; wherein PD- The OS and PFS of patients with L1 CPS ≥ 5 can reach 15.
5 and 8.
5 months
.
In the
Chinese subgroup, the objective response rate (ORR) of the nivolumab combined chemotherapy group reached 59% [4], compared with the traditional chemotherapy era The ORR of 35%-45% increased by nearly 20%; and the duration of remission (DoR) reached more than 12 months
.
“This shows that patients with advanced gastric cancer can get tumor regression with a high probability through first-line immunotherapy, and they can get a long time.
Disease control, and the quality of life of patients during this period of time is also very good
.
"Professor Zhang Xiaotian added analysis
.
At the
safety level, no new safety signals were observed in the CheckMate-649 study, and the incidence of treatment-related adverse events (TRAEs) in some patients with PD-L1 CPS≥5 is similar to that of all patients
.
For China The more important information for patients is that among all patients in the Chinese subgroup who received nivolumab combined with chemotherapy, no one died due to treatment-related adverse reactions
.
Ingenious design, the overall survival benefit fully covers CheckMate- The 649 study adopted a clever design
.
Although OS was used as a secondary endpoint in the study, the alpha value was also assigned at the beginning of the study, so that the difference achieved for each endpoint was statistically significant
.
Thanks to this, the first-line treatment indications approved for this immunotherapy combination in the United States and China eventually covered all patients with advanced gastric cancer
.
"The basic premise that China and the United States can approve the indication for the whole population is the same: the OS benefit of the whole population is not the concomitant event observed after all the alpha values are assigned to the primary research endpoint.
This is a reasonable requirement in statistical principles.
.
"but Professor Zhang Xiaotian analysis:" give the whole crowd indications, focusing on the United States and China considerations there may be different, better performance of Chinese subgroup data should also consider the Chinese regulatory authorities
.
"" because the Chinese gastric cancer The onset of disease is characterized by late discovery, late staging, large tumor burden at the time of diagnosis, and relatively poor physical status.
Such patients need to reduce tumor burden as soon as possible
.
From this perspective, for the entire clinical practice in China, this is recommended for the entire population A treatment with relatively strong curative effect does have its reason
.
"Multiple breakthroughs benefit the upper gastrointestinal tract More treatments In addition to gastric cancer, in recent years, nivolumab-based therapies have also continuously made breakthroughs in the research of high-incidence esophageal cancer in China.
.
For example, the CheckMate-648 study showed that nivolumab + chemotherapy, nivolumumab + ipilimumab for first-line treatment of advanced esophageal squamous cell carcinoma, compared with standard chemotherapy, can achieve significant OS benefits, and regardless of the patient's PD-L1 Expression level (for specific research data, please refer to → 2021 ASCO Annual Meeting Report LBA Research CheckMate-648)
.
"China's esophageal cancer is quite different from global esophageal cancer.
Squamous cell carcinoma is the majority.
The CheckMate-648 study mainly included patients with esophageal squamous cell carcinoma.
This is a very important reference for the treatment of esophageal squamous cell carcinoma in China, " said Professor Zhang Xiaotian
.
.
Based on the research results of CheckMate-649 and CheckMate-648, nivolumab became the first and currently the only first-line confirmed treatment for various histological types (squamous cell carcinoma, adenocarcinoma) and tumor sites (stomach, esophagus, gastroesophageal junction) ) Of upper gastrointestinal tumors, all PD-1/PD-L1 inhibitors with significant OS benefit
.
In addition, the CheckMate-577 study provides new ideas for postoperative adjuvant treatment of patients with esophageal cancer
.
Studies have shown that nivolumab adjuvant treatment of esophageal cancer and gastroesophageal junction cancer after neoadjuvant concurrent chemoradiation and surgery can double the disease-free survival (DFS) of patients compared with placebo
.
Based on the results of CheckMate-577, nivolumab has been approved by the U.
S.
Food and Drug Administration (FDA) in May 2021, becoming the world's first immunotherapy for adjuvant treatment of esophageal cancer
.
From the late stage to the first-line stage, to adjuvant treatment during the perioperative period, with the accumulation of more research data, nivolumab-based immunotherapy will benefit more patients with upper gastrointestinal tumors
.
Expert profile Professor Zhang Xiaotian, Peking University Cancer Hospital, Peking University Cancer Hospital, Deputy Director of International Cooperation and Exchange Department, Executive Deputy Director of Internal Medicine Teaching and Research Office Doctor of Medicine, Chief Physician, Associate Professor, Master Tutor, Chinese Society of Clinical Oncology Youth Expert Committee Chairman, China Member of the Executive Committee of the Clinical Oncology Society Member of the Gastric Cancer Professional Committee of the Chinese Anti-Cancer Association Member of the Evidence-Based Medicine Group of the Sixth Committee of Epidemiology Branch: Reviewer of "Journal of Clinical Oncology", "Chinese Journal of Oncology", "Chinese Medical Journal", and editorial board member of "Chinese Journal of Clinical Nutrition" and "Chinese Medical Journal of Chinese People's Liberation Army"; Responsible for more than ten phase II and phase III international multi-center clinical studies and a number of domestic phase II and phase III clinical studies; published more than ten SCI articles and dozens of core journals; participated in the compilation of the monograph "Advanced Oncology Course", etc.
.
References[1]Janjigian YY, Shitara K, Moehler M, et al.
First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial[J].
The Lancet, 2021, 398(10294): 27-40.
[2]Shen, L.
et.
al.
2021, First-line nivolumab plus chemotherapy versus chemotherapy in patients with advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis, AACR 2021, presentation number CT184, April 2021.
*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform
