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*Only for medical professionals to read and refer to the 2021 CSCO BC bulletin: Current status and future of breast cancer immunotherapy.
Recently, the 2021 National Breast Cancer Conference and the Chinese Society of Clinical Oncology Breast Cancer (CSCO BC) Annual Meeting opened successfully in Beijing.
The CSCO BC Annual Conference is one of the most influential academic events in the field of breast cancer in China, and it is the vane and source of motivation for the development of the discipline.
In this meeting, Professor Liu Qiang from Sun Yat-sen Memorial Hospital of Sun Yat-sen University shared wonderful reports and opinions on the development history, actual efficacy, and future opportunities and challenges of breast cancer immunotherapy.
Professor Liu Qiang reported why breast cancer needs immunotherapy? The latest cancer statistics in 2020 show that about 680,000 people die of breast cancer each year in the world.
Although breast cancer patients have a relatively good survival prognosis compared with other malignant tumors, there is still much room for improvement in the efficacy of treatment.
However, traditional treatment modes such as surgery, radiotherapy, chemotherapy, endocrine therapy, and targeted therapy have been difficult to greatly improve the survival prognosis of breast cancer patients, especially advanced patients.
As a new treatment method, immunotherapy is expected to further improve the survival rate of breast cancer patients.
In this report, Professor Liu Qiang also pointed out that the past treatments of breast cancer, including surgery, radiotherapy, chemotherapy, endocrine therapy and targeted therapy, were all aimed at tumor cells, which were meant to "eliminate evil", and because tumor cells were extremely "cunning" , Chemotherapy, endocrine therapy and targeted therapy will almost inevitably appear drug resistance in the late stage.
The immunotherapy belongs to the "strengthening", that is, the unchanging autoimmune system is used to deal with the fickle tumor cells, turning passive into active, so it is strategically superior.
Current status and new research progress of immunotherapy in breast cancer.
In the early study KEYNOTE-086, the results showed that PD-1/PD-L1 monotherapy has a certain effect on metastatic triple-negative breast cancer (mTNBC), but the tumor The remission rate is only 5-26%; the KEYNOTE-119 study compared the efficacy of pembrolizumab vs.
chemotherapy in the second and third-line treatment of mTNBC patients.
The results showed that only in patients with PD-L1 positive (CPS ≥ 20), pembrolide Razizumab can prolong the overall survival (OS) of patients compared with chemotherapy.
The above research results show that in the immunotherapy of breast cancer, the effect of PD-1/PD-L1 monotherapy is limited, and the earlier it is applied, the more likely it is for patients to benefit from immunotherapy.
In the combined application, immune combined chemotherapy is the most common, followed by the combination with targeted therapy.
Chemotherapy can induce a variety of immunomodulatory changes in the tumor microenvironment, such as increasing the release of tumor antigens, and upregulating the expression of PD-L1 and markers on the surface of immunogenic cells, thereby affecting the effect of immunotherapy.
The IMpassion130 study aims to explore the first-line treatment of atilizumab combined with albumin paclitaxel for the first-line treatment of mTNBC.
The results show that compared with albumin paclitaxel alone, atclizumab + albumin paclitaxel can significantly prolong the progression-free survival of patients Period (PFS) and OS, PFS is extended by 2.
5 months, OS is extended by 7 months; due to the continuous effect of immunotherapy, the patient's OS benefit is more obvious.
The KEYNOTE-355 study evaluated the efficacy of pembrolizumab combined with chemotherapy in the first-line treatment of mTNBC.
The results showed that pembrolizumab + chemotherapy compared with chemotherapy alone can significantly improve the PFS of patients.
With the increase of PD-L1 expression level, pembrolizumab The therapeutic effect of the benzumab + chemotherapy regimen is also enhanced.
In TNBC patients with PD-L1 CPS≥10, pembrolizumab+chemotherapy prolonged PFS by nearly 4.
1 months compared with chemotherapy alone.
Based on the considerable therapeutic effects of immunotherapy, the US FDA has approved atelizumab or pembrolizumab combined chemotherapy regimens for locally recurring unresectable or metastatic PD-L1-positive TNBC patients.
It should be noted that not all chemotherapy combined with immunotherapy can improve the survival of breast cancer patients.
In the IMpassion131 study, paclitaxel combined with atilizumab failed to significantly improve the PFS of PD-L1-positive mTNBC patients.
Therefore, the US FDA issued a warning on September 8, 2020, stating that atilizumab + paclitaxel is not suitable for TNBC Treatment of patients.
The main reason for the negative results of the study may be that the administration of paclitaxel requires the addition of hormones, and the application of hormones can interfere with the efficacy of immunotherapy, which also suggests that hormone drugs should be avoided when applying immunotherapy.
The combined application of immunotherapy and targeted therapy also has preliminary results in breast cancer.
The KEYNOTE-014 study evaluated the efficacy of pembrolizumab combined with trastuzumab in the treatment of patients with HER2+ advanced breast cancer.
The results showed that pembrolizumab+trastuzumab had a good OS in PD-L1 positive patients.
In addition, in the KATE2 study, atezizumab combined with T-DM1 compared to T-DM1 alone can extend the median PFS of patients with PD-L1-positive HER2+ advanced breast cancer from 4.
1 months to 8.
6 months.
A clinical study designed by the team of Academician Song Erwei from Sun Yat-sen Memorial Hospital of Sun Yat-Sen University and Professor Liu Qiang based on their previous translational research results to explore a chemotherapy-free regimen of anti-angiogenesis combined immunotherapy (apatinib combined with carrelizumab) The application in patients with advanced TNBC has achieved amazing results.
The data show that apatinib combined with carrelizumab can significantly improve the patient’s objective disease response rate (ORR) and prolong the survival of the patient; the results of a recent analysis showed that in addition to 10% of the patients lost to follow-up, 20% of the patients The patients are still alive, and the OS is more than two years.
10% of the patients are still taking the drug so far, and their PFS is 38, 31 and 28 months, respectively.
Professor Liu Qiang also showed an improved version based on the program, and even the brain metastasis, lung metastasis or liver metastasis of some advanced triple-negative breast cancer patients disappeared completely, bringing these patients a new hope of life.
Currently, immunotherapy is mostly used in patients with advanced TNBC.
What is the effect on hormone receptor positive (HR+) patients? A 2019 ASCO study evaluated eribulin combined with pembrolizumab in the treatment of advanced HR+ breast cancer patients.
The results showed that eribulin combined with pembrolizumab did not significantly improve the PFS and OS of patients.
The study suggests that immunotherapy may not be suitable for breast cancer patients with advanced HR+, and clinical use may do more harm than good.
However, the results of the I-SPY2 study showed that compared with chemotherapy alone, immune combination chemotherapy can significantly improve the PCR rate of early HR+ breast cancer patients, suggesting that it may be caused by the significantly different immune microenvironment of early and late HR+ breast cancer.
The current early stage The Phase III clinical trial Keynote756 is still in progress.
Can immunotherapy be used for early TNBC patients? Based on the results of current clinical trials, neoadjuvant immunotherapy for early TNBC patients can mostly increase the pathological complete remission (pCR) rate, and does not depend on the expression of PD-L1, which suggests that early and late breast cancer tumors are microscopic The environment may be significantly different, but the impact of neoadjuvant immunotherapy on the PFS and OS of patients with early TNBC is not clear; moreover, it is necessary to pay attention to the lifetime side effects of immunotherapy, some of which are more serious, and the benefits and risks need to be weighed in clinical application.
The direction and challenge of breast cancer immunotherapy Immunotherapy is the hope of improving the survival of patients with advanced breast cancer, especially TNBC patients, but it is necessary to achieve the best balance of efficacy, toxicity and tolerability in clinical practice; at present, more is needed Clinical research explores more effective immunotherapy combinations and more effective biomarkers to identify benefiting groups; in addition, the impact of targeted therapy and immune checkpoint inhibitors on the immune system requires a deeper understanding and exploration.
The ongoing clinical research of circulating tumor DNA by Professor Liu Qiang's research group can accurately screen out early triple-negative breast cancer with a high risk of recurrence, and provide corresponding enhanced treatment or monitoring, which is expected to significantly increase the cure rate of triple-negative breast cancer.
Finally, Professor Liu Qiang summarized the report: (1) The current curative effect of breast cancer is not satisfactory, and the mortality rate of patients is still high; unlike traditional treatment methods, immunotherapy can mobilize self-immunity to achieve the purpose of killing tumors.
(2) Immunotherapy is the future research direction, especially the combination with antivascular drugs and chemotherapy; in the combination therapy, the mainstay is simultaneous therapy; (3) The current immunotherapy is mainly used for advanced breast cancer, TNBC It is a hot spot for immunotherapy; for HER2+ breast cancer, immunotherapy is being tried, but there is still a lack of convincing data; for ER+ breast cancer, immunotherapy should be used with caution.
Recently, the 2021 National Breast Cancer Conference and the Chinese Society of Clinical Oncology Breast Cancer (CSCO BC) Annual Meeting opened successfully in Beijing.
The CSCO BC Annual Conference is one of the most influential academic events in the field of breast cancer in China, and it is the vane and source of motivation for the development of the discipline.
In this meeting, Professor Liu Qiang from Sun Yat-sen Memorial Hospital of Sun Yat-sen University shared wonderful reports and opinions on the development history, actual efficacy, and future opportunities and challenges of breast cancer immunotherapy.
Professor Liu Qiang reported why breast cancer needs immunotherapy? The latest cancer statistics in 2020 show that about 680,000 people die of breast cancer each year in the world.
Although breast cancer patients have a relatively good survival prognosis compared with other malignant tumors, there is still much room for improvement in the efficacy of treatment.
However, traditional treatment modes such as surgery, radiotherapy, chemotherapy, endocrine therapy, and targeted therapy have been difficult to greatly improve the survival prognosis of breast cancer patients, especially advanced patients.
As a new treatment method, immunotherapy is expected to further improve the survival rate of breast cancer patients.
In this report, Professor Liu Qiang also pointed out that the past treatments of breast cancer, including surgery, radiotherapy, chemotherapy, endocrine therapy and targeted therapy, were all aimed at tumor cells, which were meant to "eliminate evil", and because tumor cells were extremely "cunning" , Chemotherapy, endocrine therapy and targeted therapy will almost inevitably appear drug resistance in the late stage.
The immunotherapy belongs to the "strengthening", that is, the unchanging autoimmune system is used to deal with the fickle tumor cells, turning passive into active, so it is strategically superior.
Current status and new research progress of immunotherapy in breast cancer.
In the early study KEYNOTE-086, the results showed that PD-1/PD-L1 monotherapy has a certain effect on metastatic triple-negative breast cancer (mTNBC), but the tumor The remission rate is only 5-26%; the KEYNOTE-119 study compared the efficacy of pembrolizumab vs.
chemotherapy in the second and third-line treatment of mTNBC patients.
The results showed that only in patients with PD-L1 positive (CPS ≥ 20), pembrolide Razizumab can prolong the overall survival (OS) of patients compared with chemotherapy.
The above research results show that in the immunotherapy of breast cancer, the effect of PD-1/PD-L1 monotherapy is limited, and the earlier it is applied, the more likely it is for patients to benefit from immunotherapy.
In the combined application, immune combined chemotherapy is the most common, followed by the combination with targeted therapy.
Chemotherapy can induce a variety of immunomodulatory changes in the tumor microenvironment, such as increasing the release of tumor antigens, and upregulating the expression of PD-L1 and markers on the surface of immunogenic cells, thereby affecting the effect of immunotherapy.
The IMpassion130 study aims to explore the first-line treatment of atilizumab combined with albumin paclitaxel for the first-line treatment of mTNBC.
The results show that compared with albumin paclitaxel alone, atclizumab + albumin paclitaxel can significantly prolong the progression-free survival of patients Period (PFS) and OS, PFS is extended by 2.
5 months, OS is extended by 7 months; due to the continuous effect of immunotherapy, the patient's OS benefit is more obvious.
The KEYNOTE-355 study evaluated the efficacy of pembrolizumab combined with chemotherapy in the first-line treatment of mTNBC.
The results showed that pembrolizumab + chemotherapy compared with chemotherapy alone can significantly improve the PFS of patients.
With the increase of PD-L1 expression level, pembrolizumab The therapeutic effect of the benzumab + chemotherapy regimen is also enhanced.
In TNBC patients with PD-L1 CPS≥10, pembrolizumab+chemotherapy prolonged PFS by nearly 4.
1 months compared with chemotherapy alone.
Based on the considerable therapeutic effects of immunotherapy, the US FDA has approved atelizumab or pembrolizumab combined chemotherapy regimens for locally recurring unresectable or metastatic PD-L1-positive TNBC patients.
It should be noted that not all chemotherapy combined with immunotherapy can improve the survival of breast cancer patients.
In the IMpassion131 study, paclitaxel combined with atilizumab failed to significantly improve the PFS of PD-L1-positive mTNBC patients.
Therefore, the US FDA issued a warning on September 8, 2020, stating that atilizumab + paclitaxel is not suitable for TNBC Treatment of patients.
The main reason for the negative results of the study may be that the administration of paclitaxel requires the addition of hormones, and the application of hormones can interfere with the efficacy of immunotherapy, which also suggests that hormone drugs should be avoided when applying immunotherapy.
The combined application of immunotherapy and targeted therapy also has preliminary results in breast cancer.
The KEYNOTE-014 study evaluated the efficacy of pembrolizumab combined with trastuzumab in the treatment of patients with HER2+ advanced breast cancer.
The results showed that pembrolizumab+trastuzumab had a good OS in PD-L1 positive patients.
In addition, in the KATE2 study, atezizumab combined with T-DM1 compared to T-DM1 alone can extend the median PFS of patients with PD-L1-positive HER2+ advanced breast cancer from 4.
1 months to 8.
6 months.
A clinical study designed by the team of Academician Song Erwei from Sun Yat-sen Memorial Hospital of Sun Yat-Sen University and Professor Liu Qiang based on their previous translational research results to explore a chemotherapy-free regimen of anti-angiogenesis combined immunotherapy (apatinib combined with carrelizumab) The application in patients with advanced TNBC has achieved amazing results.
The data show that apatinib combined with carrelizumab can significantly improve the patient’s objective disease response rate (ORR) and prolong the survival of the patient; the results of a recent analysis showed that in addition to 10% of the patients lost to follow-up, 20% of the patients The patients are still alive, and the OS is more than two years.
10% of the patients are still taking the drug so far, and their PFS is 38, 31 and 28 months, respectively.
Professor Liu Qiang also showed an improved version based on the program, and even the brain metastasis, lung metastasis or liver metastasis of some advanced triple-negative breast cancer patients disappeared completely, bringing these patients a new hope of life.
Currently, immunotherapy is mostly used in patients with advanced TNBC.
What is the effect on hormone receptor positive (HR+) patients? A 2019 ASCO study evaluated eribulin combined with pembrolizumab in the treatment of advanced HR+ breast cancer patients.
The results showed that eribulin combined with pembrolizumab did not significantly improve the PFS and OS of patients.
The study suggests that immunotherapy may not be suitable for breast cancer patients with advanced HR+, and clinical use may do more harm than good.
However, the results of the I-SPY2 study showed that compared with chemotherapy alone, immune combination chemotherapy can significantly improve the PCR rate of early HR+ breast cancer patients, suggesting that it may be caused by the significantly different immune microenvironment of early and late HR+ breast cancer.
The current early stage The Phase III clinical trial Keynote756 is still in progress.
Can immunotherapy be used for early TNBC patients? Based on the results of current clinical trials, neoadjuvant immunotherapy for early TNBC patients can mostly increase the pathological complete remission (pCR) rate, and does not depend on the expression of PD-L1, which suggests that early and late breast cancer tumors are microscopic The environment may be significantly different, but the impact of neoadjuvant immunotherapy on the PFS and OS of patients with early TNBC is not clear; moreover, it is necessary to pay attention to the lifetime side effects of immunotherapy, some of which are more serious, and the benefits and risks need to be weighed in clinical application.
The direction and challenge of breast cancer immunotherapy Immunotherapy is the hope of improving the survival of patients with advanced breast cancer, especially TNBC patients, but it is necessary to achieve the best balance of efficacy, toxicity and tolerability in clinical practice; at present, more is needed Clinical research explores more effective immunotherapy combinations and more effective biomarkers to identify benefiting groups; in addition, the impact of targeted therapy and immune checkpoint inhibitors on the immune system requires a deeper understanding and exploration.
The ongoing clinical research of circulating tumor DNA by Professor Liu Qiang's research group can accurately screen out early triple-negative breast cancer with a high risk of recurrence, and provide corresponding enhanced treatment or monitoring, which is expected to significantly increase the cure rate of triple-negative breast cancer.
Finally, Professor Liu Qiang summarized the report: (1) The current curative effect of breast cancer is not satisfactory, and the mortality rate of patients is still high; unlike traditional treatment methods, immunotherapy can mobilize self-immunity to achieve the purpose of killing tumors.
(2) Immunotherapy is the future research direction, especially the combination with antivascular drugs and chemotherapy; in the combination therapy, the mainstay is simultaneous therapy; (3) The current immunotherapy is mainly used for advanced breast cancer, TNBC It is a hot spot for immunotherapy; for HER2+ breast cancer, immunotherapy is being tried, but there is still a lack of convincing data; for ER+ breast cancer, immunotherapy should be used with caution.
