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*Only for medical professionals to read and refer to Professor Zhang Xiaotian's in-depth analysis of the interim analysis results of the KEYNOTE-811 study
.
The incidence of gastric cancer in China accounts for about 50% of the world's total, and about 80% of patients are already in the advanced stage when they are diagnosed.
There are few treatment options and limited efficacy
.
In 2010, trastuzumab was shown to improve the efficacy of HER-2 positive gastric cancer, leading the treatment of gastric cancer into a targeted era
.
With the advent of the age of immunotherapy, immune checkpoint inhibitors have brought new options for patients with advanced gastric cancer
.
In May 2021, the U.
S.
Food and Drug Administration (FDA) accelerated the approval of pembrolizumab combined with trastuzumab and chemotherapy for the first-line treatment of HER-2 positive advanced gastric cancer based on the results of the KEYNOTE-811 study.
Pembrolizumab has become the world's first and currently the only PD-(L)1 inhibitor used in the first-line treatment of patients with this type of gastric cancer
.
The KEYNOTE-811 study is a randomized, double-blind, placebo-controlled phase III study to evaluate pembrolizumab combined with trastuzumab and chemotherapy for the first-line treatment of HER-2 positive unresectable or metastatic gastric cancer/stomach Efficacy and safety of adenocarcinoma at the junction of the esophagus
.
The study included 692 patients who were randomly assigned to the pembrolizumab+trastuzumab+chemotherapy group and the placebo+trastuzumab+chemotherapy group at 1:1
.
The study set dual primary endpoints, including overall survival (OS) and progression-free survival (PFS) assessed by the blinded independent central review committee (BICR) according to RECIST v1.
1
.
Secondary endpoints include the objective response rate (ORR) and duration of response (DOR) and safety assessed by BICR according to RECIST v1.
1
.
Figure 1.
KEYNOTE-811 research design.
At the just-concluded 2021 American Society of Clinical Oncology (ASCO) annual meeting, the KEYNOTE-811 research released the latest data.
The Medical Oncology Channel specially invited Professor Zhang Xiaotian from Peking University Cancer Hospital to interpret it for us Data analysis results, and share personal views on the significance of this research for the current and future clinical practice of advanced gastric cancer precision diagnosis and treatment in China
.
Professor Zhang Xiaotian’s wonderful video.
First-line immunotherapy significantly improves ORR and CR, which is suggestive for neoadjuvant and conversion therapy for early gastric cancer.
Professor Zhang Xiaotian: Interim analysis results of the KEYNOTE-811 study show that pembrolizumab + trastuzumab + The ORR of the chemotherapy group was as high as 74.
4%, and the complete remission rate (CR) was nearly 4 times that of the control group, reaching 11% (3% of the control group)
.
Figure 2.
Results of the interim analysis of the KEYNOTE-811 study.
This data is in line with the data of the Phase Ib/II clinical study PANTHERA (ORR 76.
7%, CR 16.
3) for the three-drug combination treatment of HER-2 positive advanced gastric cancer in Japan released by ASCO in 2020.
%) consistent
.
In the future, we will definitely explore the therapeutic potential of this combination therapy model in the earlier stages of the disease, such as neoadjuvant therapy for locally advanced gastric cancer, or translational studies of gastric cancer with a single metastatic factor
.
Then these two groups of people must be based on the data of first-line treatment of advanced gastric cancer, specifically the ORR, DOR and CR of the treatment plan
.
These three data have particularly important hints for our earlier new assistance and conversion
.
Compared with advanced gastric cancer, the ORR and CR of locally advanced gastric cancer should be higher
.
The overall tumor burden of the Chinese population with advanced gastric cancer is high and the physical status is poor
.
Therefore, in the initial stage of treatment, there is often a need for a treatment plan that can effectively shrink the tumor.
At this time, the use of this three-drug combination treatment strategy is to "use good steel on the edge", and it has important clinical value
.
Therefore, from these perspectives, the results of the KEYNOTE-811 interim analysis released by ASCO still delivered a satisfactory answer
.
The characteristics of the enrolled population of KEYNOTE-811 are consistent with those of Chinese patients.
Professor Zhang Xiaotian: Analysis of the characteristics of the enrolled population found that nearly 90% of the patients had PD-L1 CPS ≥ 1, and HER-2+ patients were mainly IHC 3+ (82 %), the pathological characteristics are similar to those of Chinese gastric cancer patients
.
I will look forward to seeing the data on the tumor burden and physical status of the research population in the future.
If it is similar to the Chinese gastric cancer population, then I will be more confident that the KEYNOTE-811 research data is meaningful for guiding clinical practice in China
.
Figure 3.
Baseline characteristics of KEYNOTE-811 study population.
In addition, KEYNOTE-811 enrolled population of peritoneal metastasis, liver metastasis and other different metastatic organ characteristics, as well as HER-2 (3+), PDL-1 positive, cardia intestinal type This part of HER-2 is strongly positive, and whether the PD-L1 population will have more significant OS benefits will also help determine the significance of KEYNOTE-811 in clinical practice in China
.
The clinical application value of the three-drug combination therapy strategy is significant, and we look forward to follow-up OS benefit analysis.
Professor Zhang Xiaotian: For advanced gastric cancer, the pursuit of clinical treatment has always been to make patients live longer and better
.
In the KEYNOTE-811 study, combined immunotherapy significantly improved ORR, but the OS data has not been analyzed yet; and we also need to consider that the control group received late-line immunotherapy after disease progression, or has been obtained at home and abroad.
Antibody-conjugated drug (ADC) therapy for the post-approval treatment of HER-2 positive advanced gastric cancer will "interference" the final OS result of KEYNOTE-811
.
Therefore, whether it is the improvement of ORR or the improvement of these indicators of PFS and DOR, because its initial advantage may be equalized by other follow-up treatments, subsequent analysis of OS data is still worth looking forward to
.
I personally think that pembrolizumab combined with trastuzumab and chemotherapy are very important treatment options for HER-2 positive advanced gastric cancer, especially for patients with HER-2 IHC3+ and PD-L1 positive cardia intestines
.
We look forward to a year later, KEYNOTE-811 can bring us positive results of PFS and OS
.
Standardize routine HER-2 testing and improve the level of standardized diagnosis and treatment of gastric cancer in China Professor Zhang Xiaotian: Since trastuzumab has been used in clinical practice, clinicians have continued to deepen their understanding of HER-2 testing, but there are still some doctors and patients in the treatment The HER-2 test results were not clear before, or repeated tests were not performed during the treatment process, resulting in some patients with HER-2 positive advanced gastric cancer not receiving standardized treatment
.
With the introduction of new drugs and new research, we should pay more attention to HER-2 testing, not only testing before the initial treatment of the disease, but also by retesting the status of HER-2 during the treatment process and when the patient’s disease progresses.
HER-2 treatment is more refined management
.
Both the National Cancer Comprehensive Network (NCCN) and the Chinese Society of Clinical Oncology (CSCO) guidelines propose that routine HER-2 testing must be carried out for gastric adenocarcinoma
.
The HER-2 test must first attract the attention of doctors, and secondly, it must be supported by the hospital management department, pathology department, surgery, gastroenterology, and endoscopy team
.
In clinical practice, the most common difficulty encountered in HER-2 testing is that gastric cancer is considered in the diagnosis of gastroscopy.
However, many hospitals will not apply for HER-2 testing before the pathological diagnosis is confirmed, and perform HER-2 after the pathological diagnosis is confirmed.
The test needs to wait for a while, so some patients in clinical practice have started treatment before the HER-2 test result is available
.
In order to save the patient's time to the greatest extent, in the case of full communication with the hospital management department and the pathology department, it is possible to apply for pathology and HER-2 testing at the same time when gastric cancer is considered for gastroscopy diagnosis
.
For patients with gastric cancer, the detection of HER-2 positive is undoubtedly an increase in treatment opportunities.
It is hoped that doctors and patients can seize this opportunity and allow more patients to benefit from standardized diagnosis and treatment
.
Expert profile Professor Zhang Xiaotian, Doctor of Medicine, Chief Physician, Associate Professor, Master Tutor, Department of Digestive Oncology, Peking University Cancer Hospital, Deputy Director, International Cooperation and Exchange Department, Peking University Cancer Hospital, Executive Deputy Director, Internal Medicine Teaching and Research Office, Chairman of the Youth Expert Committee of the Chinese Society of Clinical Oncology, China Clinic Member of the Executive Committee of the Oncology Society Member of the Gastric Cancer Professional Committee of the Chinese Anti-Cancer Association Secretary-General of the Cancer Nutrition Therapy and Support Committee of the Chinese Anti-Cancer Association Leader of the Chemotherapy Nutrition Group Member of the Gastrointestinal Subcommittee of the Geriatric Oncology Professional Committee of the Chinese Society of Geriatrics Member of the Evidence-based Medicine Group of the Sixth Committee of the Division of Diseases, Reviewer of "Journal of Clinical Oncology", "Chinese Journal of Oncology", "Chinese Medical Journal", editorial board member of "Chinese Journal of Clinical Nutrition" and "Medical Journal of Chinese People's Liberation Army"; in charge; more than ten II, international multi-center phase III clinical studies and a number of domestic II, III clinical studies; SCI published more than thirty articles, dozens of core journals; monographs "Oncology advanced tutorial" and so on
.
*This article is only used to provide scientific information to medical professionals, and does not represent the views of this platform
.
The incidence of gastric cancer in China accounts for about 50% of the world's total, and about 80% of patients are already in the advanced stage when they are diagnosed.
There are few treatment options and limited efficacy
.
In 2010, trastuzumab was shown to improve the efficacy of HER-2 positive gastric cancer, leading the treatment of gastric cancer into a targeted era
.
With the advent of the age of immunotherapy, immune checkpoint inhibitors have brought new options for patients with advanced gastric cancer
.
In May 2021, the U.
S.
Food and Drug Administration (FDA) accelerated the approval of pembrolizumab combined with trastuzumab and chemotherapy for the first-line treatment of HER-2 positive advanced gastric cancer based on the results of the KEYNOTE-811 study.
Pembrolizumab has become the world's first and currently the only PD-(L)1 inhibitor used in the first-line treatment of patients with this type of gastric cancer
.
The KEYNOTE-811 study is a randomized, double-blind, placebo-controlled phase III study to evaluate pembrolizumab combined with trastuzumab and chemotherapy for the first-line treatment of HER-2 positive unresectable or metastatic gastric cancer/stomach Efficacy and safety of adenocarcinoma at the junction of the esophagus
.
The study included 692 patients who were randomly assigned to the pembrolizumab+trastuzumab+chemotherapy group and the placebo+trastuzumab+chemotherapy group at 1:1
.
The study set dual primary endpoints, including overall survival (OS) and progression-free survival (PFS) assessed by the blinded independent central review committee (BICR) according to RECIST v1.
1
.
Secondary endpoints include the objective response rate (ORR) and duration of response (DOR) and safety assessed by BICR according to RECIST v1.
1
.
Figure 1.
KEYNOTE-811 research design.
At the just-concluded 2021 American Society of Clinical Oncology (ASCO) annual meeting, the KEYNOTE-811 research released the latest data.
The Medical Oncology Channel specially invited Professor Zhang Xiaotian from Peking University Cancer Hospital to interpret it for us Data analysis results, and share personal views on the significance of this research for the current and future clinical practice of advanced gastric cancer precision diagnosis and treatment in China
.
Professor Zhang Xiaotian’s wonderful video.
First-line immunotherapy significantly improves ORR and CR, which is suggestive for neoadjuvant and conversion therapy for early gastric cancer.
Professor Zhang Xiaotian: Interim analysis results of the KEYNOTE-811 study show that pembrolizumab + trastuzumab + The ORR of the chemotherapy group was as high as 74.
4%, and the complete remission rate (CR) was nearly 4 times that of the control group, reaching 11% (3% of the control group)
.
Figure 2.
Results of the interim analysis of the KEYNOTE-811 study.
This data is in line with the data of the Phase Ib/II clinical study PANTHERA (ORR 76.
7%, CR 16.
3) for the three-drug combination treatment of HER-2 positive advanced gastric cancer in Japan released by ASCO in 2020.
%) consistent
.
In the future, we will definitely explore the therapeutic potential of this combination therapy model in the earlier stages of the disease, such as neoadjuvant therapy for locally advanced gastric cancer, or translational studies of gastric cancer with a single metastatic factor
.
Then these two groups of people must be based on the data of first-line treatment of advanced gastric cancer, specifically the ORR, DOR and CR of the treatment plan
.
These three data have particularly important hints for our earlier new assistance and conversion
.
Compared with advanced gastric cancer, the ORR and CR of locally advanced gastric cancer should be higher
.
The overall tumor burden of the Chinese population with advanced gastric cancer is high and the physical status is poor
.
Therefore, in the initial stage of treatment, there is often a need for a treatment plan that can effectively shrink the tumor.
At this time, the use of this three-drug combination treatment strategy is to "use good steel on the edge", and it has important clinical value
.
Therefore, from these perspectives, the results of the KEYNOTE-811 interim analysis released by ASCO still delivered a satisfactory answer
.
The characteristics of the enrolled population of KEYNOTE-811 are consistent with those of Chinese patients.
Professor Zhang Xiaotian: Analysis of the characteristics of the enrolled population found that nearly 90% of the patients had PD-L1 CPS ≥ 1, and HER-2+ patients were mainly IHC 3+ (82 %), the pathological characteristics are similar to those of Chinese gastric cancer patients
.
I will look forward to seeing the data on the tumor burden and physical status of the research population in the future.
If it is similar to the Chinese gastric cancer population, then I will be more confident that the KEYNOTE-811 research data is meaningful for guiding clinical practice in China
.
Figure 3.
Baseline characteristics of KEYNOTE-811 study population.
In addition, KEYNOTE-811 enrolled population of peritoneal metastasis, liver metastasis and other different metastatic organ characteristics, as well as HER-2 (3+), PDL-1 positive, cardia intestinal type This part of HER-2 is strongly positive, and whether the PD-L1 population will have more significant OS benefits will also help determine the significance of KEYNOTE-811 in clinical practice in China
.
The clinical application value of the three-drug combination therapy strategy is significant, and we look forward to follow-up OS benefit analysis.
Professor Zhang Xiaotian: For advanced gastric cancer, the pursuit of clinical treatment has always been to make patients live longer and better
.
In the KEYNOTE-811 study, combined immunotherapy significantly improved ORR, but the OS data has not been analyzed yet; and we also need to consider that the control group received late-line immunotherapy after disease progression, or has been obtained at home and abroad.
Antibody-conjugated drug (ADC) therapy for the post-approval treatment of HER-2 positive advanced gastric cancer will "interference" the final OS result of KEYNOTE-811
.
Therefore, whether it is the improvement of ORR or the improvement of these indicators of PFS and DOR, because its initial advantage may be equalized by other follow-up treatments, subsequent analysis of OS data is still worth looking forward to
.
I personally think that pembrolizumab combined with trastuzumab and chemotherapy are very important treatment options for HER-2 positive advanced gastric cancer, especially for patients with HER-2 IHC3+ and PD-L1 positive cardia intestines
.
We look forward to a year later, KEYNOTE-811 can bring us positive results of PFS and OS
.
Standardize routine HER-2 testing and improve the level of standardized diagnosis and treatment of gastric cancer in China Professor Zhang Xiaotian: Since trastuzumab has been used in clinical practice, clinicians have continued to deepen their understanding of HER-2 testing, but there are still some doctors and patients in the treatment The HER-2 test results were not clear before, or repeated tests were not performed during the treatment process, resulting in some patients with HER-2 positive advanced gastric cancer not receiving standardized treatment
.
With the introduction of new drugs and new research, we should pay more attention to HER-2 testing, not only testing before the initial treatment of the disease, but also by retesting the status of HER-2 during the treatment process and when the patient’s disease progresses.
HER-2 treatment is more refined management
.
Both the National Cancer Comprehensive Network (NCCN) and the Chinese Society of Clinical Oncology (CSCO) guidelines propose that routine HER-2 testing must be carried out for gastric adenocarcinoma
.
The HER-2 test must first attract the attention of doctors, and secondly, it must be supported by the hospital management department, pathology department, surgery, gastroenterology, and endoscopy team
.
In clinical practice, the most common difficulty encountered in HER-2 testing is that gastric cancer is considered in the diagnosis of gastroscopy.
However, many hospitals will not apply for HER-2 testing before the pathological diagnosis is confirmed, and perform HER-2 after the pathological diagnosis is confirmed.
The test needs to wait for a while, so some patients in clinical practice have started treatment before the HER-2 test result is available
.
In order to save the patient's time to the greatest extent, in the case of full communication with the hospital management department and the pathology department, it is possible to apply for pathology and HER-2 testing at the same time when gastric cancer is considered for gastroscopy diagnosis
.
For patients with gastric cancer, the detection of HER-2 positive is undoubtedly an increase in treatment opportunities.
It is hoped that doctors and patients can seize this opportunity and allow more patients to benefit from standardized diagnosis and treatment
.
Expert profile Professor Zhang Xiaotian, Doctor of Medicine, Chief Physician, Associate Professor, Master Tutor, Department of Digestive Oncology, Peking University Cancer Hospital, Deputy Director, International Cooperation and Exchange Department, Peking University Cancer Hospital, Executive Deputy Director, Internal Medicine Teaching and Research Office, Chairman of the Youth Expert Committee of the Chinese Society of Clinical Oncology, China Clinic Member of the Executive Committee of the Oncology Society Member of the Gastric Cancer Professional Committee of the Chinese Anti-Cancer Association Secretary-General of the Cancer Nutrition Therapy and Support Committee of the Chinese Anti-Cancer Association Leader of the Chemotherapy Nutrition Group Member of the Gastrointestinal Subcommittee of the Geriatric Oncology Professional Committee of the Chinese Society of Geriatrics Member of the Evidence-based Medicine Group of the Sixth Committee of the Division of Diseases, Reviewer of "Journal of Clinical Oncology", "Chinese Journal of Oncology", "Chinese Medical Journal", editorial board member of "Chinese Journal of Clinical Nutrition" and "Medical Journal of Chinese People's Liberation Army"; in charge; more than ten II, international multi-center phase III clinical studies and a number of domestic II, III clinical studies; SCI published more than thirty articles, dozens of core journals; monographs "Oncology advanced tutorial" and so on
.
*This article is only used to provide scientific information to medical professionals, and does not represent the views of this platform
