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*Only for medical professionals to read for reference.
Atelizumab is the first-line treatment for advanced NSCLC with high PD-L1 expression.
It is safe and effective, and patients are more at ease.
Lung cancer is the malignant tumor with the highest incidence and mortality in China.
Among them, non-small cell lung cancer (NSCLC) is more common, with an incidence of 80%-85% [1].
With the advent of immunotherapy, the prognosis of NSCLC patients has improved, but while immunotherapy improves survival, the immune-related adverse reactions brought about by it are also worthy of attention.
The "medical community" has the honor to invite Professor Zhang Li from Peking Union Medical College Hospital to share professionally on the management of NSCLC immunotherapy and related adverse reactions.
Pay attention to the management of immunotherapy-related adverse reactions and optimize the benefits of NSCLC.
Up to now, immunotherapy has been used in NSCLC for nearly ten years.
Initially, the international multi-center clinical research and the data of Chinese people going abroad for medical treatment showed us that immunotherapy can bring objective curative effects and survival benefits to patients.
In the past three years, with the successful listing of immunotherapy drugs at home and abroad, immunotherapy has covered the first and second lines of advanced NSCLC, which has greatly improved the prognosis of patients.
Some patients can even achieve long-term survival through simple immunotherapy, reaching a state of "small cure".
The emergence of immunotherapy has caused a fundamental change in the treatment pattern of NSCLC, but at the same time it has also brought a new spectrum of toxicity.
Compared with the adverse reactions caused by other treatments, such as radiotherapy and chemotherapy, targeted therapy, and anti-angiogenesis therapy, immunotherapy-related adverse reactions (irAEs) are insidious and not fixed, and can involve various organs throughout the body [2].
Professor Zhang Li said that the fundamental reason for the emergence of irAEs is that the addition of immunotherapy drugs breaks the patient's original balanced immune state, which can be attributed to autoimmune diseases.
With the widespread clinical application of immune checkpoint inhibitors (ICIs), clinicians need to fully understand the possible adverse effects of such drug treatments and reasonable treatment strategies to improve the survival rate and treatment effect of patients receiving ICIs[ 3].
Figure 1.
irAEs affect multiple organs and tissues throughout the body.
Professor Zhang pointed out that in the early days of immunotherapy, many international multi-center clinical studies did not clearly tell us what side effects such drugs can cause and how to deal with these side effects.
reaction.
The reason is that there are blind spots in the global understanding of irAEs.
The mechanism and treatment of irAEs are not clear, and clinicians are more dependent on clinical discovery and summary.
In recent years, domestic researchers have made a lot of efforts in irAEs.
In 2019, the team of Professor Zhang Li (hereinafter referred to as the "team") published 13 articles on the principles of irAEs handling in the Chinese Journal of Lung Cancer.
Provide oncologists with clear diagnosis and treatment recommendations for irAEs from various specialties and various systems.
In May of the same year, the team conducted a literature search of irAEs, collected more than 200 case reports, studied, discussed and commented on each case, and compiled the "Comprehensive Review of 200 Cases of Adverse Reactions Related to Immune Checkpoint Inhibitors".
Further promote the progress of irAEs management.
In addition, in 2020, the team conducted more than 100 online consultations for severe irAEs in various regions of the country.
Finally, Professor Zhang Li emphasized that improving the management of irAEs is the key to ensuring the true health of immunotherapy patients and maximizing the benefits of immunotherapy.
Atelizumab single-drug therapy brings "survival" and "quality" double guarantee for NSCLC patients.
The mechanism of action of PD-L1 inhibitors is somewhat different from that of PD-1 antibodies.
In addition to blocking PD-L1 and PD- 1 In addition to interaction, it can also bind to B7.
1 to inhibit dendritic cells from generating T cell activity and enhance immune response. The successful single-agent treatment of atilizumab reflects its excellent efficacy.
At the same time, PD-L1 inhibitors work by inhibiting PD-L1 sites and do not affect PD-1/PD-L2 The combination of, preserves immune homeostasis to a certain extent, helps prevent autoimmune reactions [4], and immune-related toxic side effects will be lower.
The IMpower110 study showed that [5], compared with traditional chemotherapy, first-line treatment with atelizumab can significantly improve the median overall survival (OS) of patients with advanced NSCLC with high PD-L1 expression.
The OS of the two groups was 20.
2 respectively.
Month and 13.
1 months (HR=0.
59, 95%CI: 0.
40-0.
89, P=0.
01).
Figure 2.
OS results of PD-L1 high-expressing WT population (main analysis) Among them, the duration of remission (DoR) of 38.
9 months attracts everyone's attention and is the longest among all immune drugs.
The ultra-long DoR just confirms the "long tail" characteristics of immunotherapy.
Once the patient gets relief from atelizumab, it is likely to obtain long-term benefits.
Figure 3.
Atelizumab first-line treatment of patients with PFS and DoR.
In terms of safety, atelizumab also has a good performance.
The data showed that the incidence of adverse events (AE) above grade 3 in the atilizumab group was significantly lower than that in the chemotherapy group, and the safety was better.
The most common irAEs in the atilizumab group were pruritus and hypothyroidism, both of which were clinically controllable.
Table 1.
Summary of IMpower110 study safety Professor Zhang Li pointed out that the IMpower110 study is unique-it is the first clinical study in which a PD-L1 inhibitor is applied to NSCLC with positive results.
The success of the IMpower110 study has established the status of PD-L1 inhibitors as the first-line treatment of NSCLC.
At present, whether it is from the previously published research data or our actual clinical application experience, PD-L1 inhibitors, especially atilizumab, have relatively low side effects.
For NSCLC patients, immune monotherapy is an alternative and promising treatment option.
Looking to the future, the application of immunotherapy in lung cancer has broad prospects.
As we all know, not all patients can benefit from immunotherapy.
From the perspective of tumor pathogenesis, almost all tumor patients have certain immune deficiencies and problems.
In the era of precision therapy, how to achieve precise prediction of the efficacy of immunotherapy and screening the best benefit population for immunotherapy is an important direction for future research.
In addition, there are some patients whose immunotherapy is effective but will relapse.
Therefore, how to achieve dynamic detection and early detection of drug-resistant populations so that both primary and secondary drug-resistant patients can be effectively managed is also an important research area.
In addition, many topics such as immunotherapy and infection, immunotherapy adverse reactions and infections, malignant tumors and infections are also urgent for us to explore.
At present, our team has also carried out preliminary work in this area, and hopes to share relevant research results with you soon .
Summary The emergence of immunotherapy has brought fundamental changes to the treatment of the entire tumor field, especially the treatment of solid tumors, but it also brought new side effects.
The PD-L1 inhibitor atelizumab single-agent treatment of NSCLC can significantly prolong the survival of patients, with a median OS of 20.
2 months, and the incidence of grade 3 or higher AEs is significantly lower than that of chemotherapy, and the safety is better, allowing patients to obtain Long-term survival also has a higher quality of life.
The approval of the NSCLC indication for atilizumab brings more choices and survival benefits for NSCLC patients in my country.
Expert profile Professor Zhang Li, chief physician of the Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, doctoral tutor, and well-known professor.
In 2015, he was awarded the “First Prize of National Science and Technology Progress Award” as the fifth complete person.
In 2017, he was awarded the Respiratory Disease Branch of Chinese Medical Association.
Outstanding Respiratory Academic Contribution Award" won the China Association for the Promotion of Pharmaceuticals, and the 2019 "Dushu Lake Cup" Pharmaceutical Innovation "Most Influential Drug Clinical Research Leader Award" 2020.
1.
22 won the first prize of Tianjin Science and Technology Progress Award 2020.
7.
25 Won the second prize of the Science and Technology Award of the Chinese Anti-Cancer Association.
Won the Hospital Medical Achievement Award for many times.
Interdisciplinary Sciences: Computational Life Sciences Associate Editor (SCI 1.
46) Member of the Lung Cancer Group of the Chinese Medical Association Member of the Chinese Lung Cancer Alliance Member of the Beijing Branch Vice Chairman of the China Lung Cancer Prevention Alliance Immunization Chairman of the Treatment Committee Beijing Medical Award Foundation Brain Metastasis Specialized Committee Deputy Chairman CACA Tumor Microenvironment Specialized Committee Standing Committee CSCO Tumor Cardiology Specialist Committee Standing Committee Member of the Chinese Thoracic Tumor Research Collaboration Group (GACT/CTONG) Member of China Medical Innovation Member of the Standing Committee of the Anti-tumor Drug Clinical Research Committee of the Promotion Association Member of the Chinese Respiratory Tumor Collaboration Group Member of the Chinese Society of Intersection Sciences Member of the Sixth Editorial Committee of Chinese Respiratory Journal Member of the Sixth Editorial Committee of Chinese Journal of Lung Cancer "Chinese Journal of Clinicians (Electronic Edition)" Expert Committee Standing Committee Member of the Internet of Things Medical Professional Committee of China Association of Non-Public Medical Institutions Standing Committee Member of the Lung Cancer Subcommittee of the Geriatric Oncology Committee of the Chinese Society of Gerontology Beijing Cancer Research Association/Lyyin Salon Cancer Research Collaboration Group member reference [1] Lei Yuanyuan, Wu Yilong.
The prognostic value of micrometastasis in non-small cell lung cancer.
Chinese Journal of Lung Cancer.
2013 No.
9 492-498.
[2] Puzanov I, et al.
J Immunother Cancer.
2017; 5:95.
[3] Duan Lian, Wang Linjie, Si Xiaoyan, et al.
Recommendations for clinical diagnosis and treatment of adverse endocrine reactions related to immune checkpoint inhibitors.
Chinese Journal of Lung Cancer.
2019; 22(10):649-652.
[4] Chen DS, Irving BA, Hodi FS.
Molecular pathways:next-generation immunotherapy--inhibiting programmed death-ligand 1 and programmed death-1[J].
Clin Cancer Res,2012 ,18(24):6580-6587.
[5] Roy S.
Herbst, Giuseppe Giaccone,et al.
Atezolizumab for First-Line Treatment of PD-L1--Selected Patients with NSCLC.
N Engl J Med 2020;383:1328-39.
Atelizumab is the first-line treatment for advanced NSCLC with high PD-L1 expression.
It is safe and effective, and patients are more at ease.
Lung cancer is the malignant tumor with the highest incidence and mortality in China.
Among them, non-small cell lung cancer (NSCLC) is more common, with an incidence of 80%-85% [1].
With the advent of immunotherapy, the prognosis of NSCLC patients has improved, but while immunotherapy improves survival, the immune-related adverse reactions brought about by it are also worthy of attention.
The "medical community" has the honor to invite Professor Zhang Li from Peking Union Medical College Hospital to share professionally on the management of NSCLC immunotherapy and related adverse reactions.
Pay attention to the management of immunotherapy-related adverse reactions and optimize the benefits of NSCLC.
Up to now, immunotherapy has been used in NSCLC for nearly ten years.
Initially, the international multi-center clinical research and the data of Chinese people going abroad for medical treatment showed us that immunotherapy can bring objective curative effects and survival benefits to patients.
In the past three years, with the successful listing of immunotherapy drugs at home and abroad, immunotherapy has covered the first and second lines of advanced NSCLC, which has greatly improved the prognosis of patients.
Some patients can even achieve long-term survival through simple immunotherapy, reaching a state of "small cure".
The emergence of immunotherapy has caused a fundamental change in the treatment pattern of NSCLC, but at the same time it has also brought a new spectrum of toxicity.
Compared with the adverse reactions caused by other treatments, such as radiotherapy and chemotherapy, targeted therapy, and anti-angiogenesis therapy, immunotherapy-related adverse reactions (irAEs) are insidious and not fixed, and can involve various organs throughout the body [2].
Professor Zhang Li said that the fundamental reason for the emergence of irAEs is that the addition of immunotherapy drugs breaks the patient's original balanced immune state, which can be attributed to autoimmune diseases.
With the widespread clinical application of immune checkpoint inhibitors (ICIs), clinicians need to fully understand the possible adverse effects of such drug treatments and reasonable treatment strategies to improve the survival rate and treatment effect of patients receiving ICIs[ 3].
Figure 1.
irAEs affect multiple organs and tissues throughout the body.
Professor Zhang pointed out that in the early days of immunotherapy, many international multi-center clinical studies did not clearly tell us what side effects such drugs can cause and how to deal with these side effects.
reaction.
The reason is that there are blind spots in the global understanding of irAEs.
The mechanism and treatment of irAEs are not clear, and clinicians are more dependent on clinical discovery and summary.
In recent years, domestic researchers have made a lot of efforts in irAEs.
In 2019, the team of Professor Zhang Li (hereinafter referred to as the "team") published 13 articles on the principles of irAEs handling in the Chinese Journal of Lung Cancer.
Provide oncologists with clear diagnosis and treatment recommendations for irAEs from various specialties and various systems.
In May of the same year, the team conducted a literature search of irAEs, collected more than 200 case reports, studied, discussed and commented on each case, and compiled the "Comprehensive Review of 200 Cases of Adverse Reactions Related to Immune Checkpoint Inhibitors".
Further promote the progress of irAEs management.
In addition, in 2020, the team conducted more than 100 online consultations for severe irAEs in various regions of the country.
Finally, Professor Zhang Li emphasized that improving the management of irAEs is the key to ensuring the true health of immunotherapy patients and maximizing the benefits of immunotherapy.
Atelizumab single-drug therapy brings "survival" and "quality" double guarantee for NSCLC patients.
The mechanism of action of PD-L1 inhibitors is somewhat different from that of PD-1 antibodies.
In addition to blocking PD-L1 and PD- 1 In addition to interaction, it can also bind to B7.
1 to inhibit dendritic cells from generating T cell activity and enhance immune response. The successful single-agent treatment of atilizumab reflects its excellent efficacy.
At the same time, PD-L1 inhibitors work by inhibiting PD-L1 sites and do not affect PD-1/PD-L2 The combination of, preserves immune homeostasis to a certain extent, helps prevent autoimmune reactions [4], and immune-related toxic side effects will be lower.
The IMpower110 study showed that [5], compared with traditional chemotherapy, first-line treatment with atelizumab can significantly improve the median overall survival (OS) of patients with advanced NSCLC with high PD-L1 expression.
The OS of the two groups was 20.
2 respectively.
Month and 13.
1 months (HR=0.
59, 95%CI: 0.
40-0.
89, P=0.
01).
Figure 2.
OS results of PD-L1 high-expressing WT population (main analysis) Among them, the duration of remission (DoR) of 38.
9 months attracts everyone's attention and is the longest among all immune drugs.
The ultra-long DoR just confirms the "long tail" characteristics of immunotherapy.
Once the patient gets relief from atelizumab, it is likely to obtain long-term benefits.
Figure 3.
Atelizumab first-line treatment of patients with PFS and DoR.
In terms of safety, atelizumab also has a good performance.
The data showed that the incidence of adverse events (AE) above grade 3 in the atilizumab group was significantly lower than that in the chemotherapy group, and the safety was better.
The most common irAEs in the atilizumab group were pruritus and hypothyroidism, both of which were clinically controllable.
Table 1.
Summary of IMpower110 study safety Professor Zhang Li pointed out that the IMpower110 study is unique-it is the first clinical study in which a PD-L1 inhibitor is applied to NSCLC with positive results.
The success of the IMpower110 study has established the status of PD-L1 inhibitors as the first-line treatment of NSCLC.
At present, whether it is from the previously published research data or our actual clinical application experience, PD-L1 inhibitors, especially atilizumab, have relatively low side effects.
For NSCLC patients, immune monotherapy is an alternative and promising treatment option.
Looking to the future, the application of immunotherapy in lung cancer has broad prospects.
As we all know, not all patients can benefit from immunotherapy.
From the perspective of tumor pathogenesis, almost all tumor patients have certain immune deficiencies and problems.
In the era of precision therapy, how to achieve precise prediction of the efficacy of immunotherapy and screening the best benefit population for immunotherapy is an important direction for future research.
In addition, there are some patients whose immunotherapy is effective but will relapse.
Therefore, how to achieve dynamic detection and early detection of drug-resistant populations so that both primary and secondary drug-resistant patients can be effectively managed is also an important research area.
In addition, many topics such as immunotherapy and infection, immunotherapy adverse reactions and infections, malignant tumors and infections are also urgent for us to explore.
At present, our team has also carried out preliminary work in this area, and hopes to share relevant research results with you soon .
Summary The emergence of immunotherapy has brought fundamental changes to the treatment of the entire tumor field, especially the treatment of solid tumors, but it also brought new side effects.
The PD-L1 inhibitor atelizumab single-agent treatment of NSCLC can significantly prolong the survival of patients, with a median OS of 20.
2 months, and the incidence of grade 3 or higher AEs is significantly lower than that of chemotherapy, and the safety is better, allowing patients to obtain Long-term survival also has a higher quality of life.
The approval of the NSCLC indication for atilizumab brings more choices and survival benefits for NSCLC patients in my country.
Expert profile Professor Zhang Li, chief physician of the Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, doctoral tutor, and well-known professor.
In 2015, he was awarded the “First Prize of National Science and Technology Progress Award” as the fifth complete person.
In 2017, he was awarded the Respiratory Disease Branch of Chinese Medical Association.
Outstanding Respiratory Academic Contribution Award" won the China Association for the Promotion of Pharmaceuticals, and the 2019 "Dushu Lake Cup" Pharmaceutical Innovation "Most Influential Drug Clinical Research Leader Award" 2020.
1.
22 won the first prize of Tianjin Science and Technology Progress Award 2020.
7.
25 Won the second prize of the Science and Technology Award of the Chinese Anti-Cancer Association.
Won the Hospital Medical Achievement Award for many times.
Interdisciplinary Sciences: Computational Life Sciences Associate Editor (SCI 1.
46) Member of the Lung Cancer Group of the Chinese Medical Association Member of the Chinese Lung Cancer Alliance Member of the Beijing Branch Vice Chairman of the China Lung Cancer Prevention Alliance Immunization Chairman of the Treatment Committee Beijing Medical Award Foundation Brain Metastasis Specialized Committee Deputy Chairman CACA Tumor Microenvironment Specialized Committee Standing Committee CSCO Tumor Cardiology Specialist Committee Standing Committee Member of the Chinese Thoracic Tumor Research Collaboration Group (GACT/CTONG) Member of China Medical Innovation Member of the Standing Committee of the Anti-tumor Drug Clinical Research Committee of the Promotion Association Member of the Chinese Respiratory Tumor Collaboration Group Member of the Chinese Society of Intersection Sciences Member of the Sixth Editorial Committee of Chinese Respiratory Journal Member of the Sixth Editorial Committee of Chinese Journal of Lung Cancer "Chinese Journal of Clinicians (Electronic Edition)" Expert Committee Standing Committee Member of the Internet of Things Medical Professional Committee of China Association of Non-Public Medical Institutions Standing Committee Member of the Lung Cancer Subcommittee of the Geriatric Oncology Committee of the Chinese Society of Gerontology Beijing Cancer Research Association/Lyyin Salon Cancer Research Collaboration Group member reference [1] Lei Yuanyuan, Wu Yilong.
The prognostic value of micrometastasis in non-small cell lung cancer.
Chinese Journal of Lung Cancer.
2013 No.
9 492-498.
[2] Puzanov I, et al.
J Immunother Cancer.
2017; 5:95.
[3] Duan Lian, Wang Linjie, Si Xiaoyan, et al.
Recommendations for clinical diagnosis and treatment of adverse endocrine reactions related to immune checkpoint inhibitors.
Chinese Journal of Lung Cancer.
2019; 22(10):649-652.
[4] Chen DS, Irving BA, Hodi FS.
Molecular pathways:next-generation immunotherapy--inhibiting programmed death-ligand 1 and programmed death-1[J].
Clin Cancer Res,2012 ,18(24):6580-6587.
[5] Roy S.
Herbst, Giuseppe Giaccone,et al.
Atezolizumab for First-Line Treatment of PD-L1--Selected Patients with NSCLC.
N Engl J Med 2020;383:1328-39.
