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*Only for medical professionals to read and reference liver cancer immunotherapy has made significant progress, and there is still room for exploration in the future.
Primary liver cancer is one of the common malignant tumors of the digestive system in China.
Its morbidity and mortality rank 6th among global cancers.
The third place, the main pathological type is hepatocellular carcinoma, accounting for about 85% [1], the overall five-year survival rate of patients with advanced liver cancer is still low
.
At the 7th BiG IMPACT Annual Conference hosted by the BiG Biomedical Innovation Society a few days ago, the "medical community" was fortunate to invite Zhu Xiuxuan, a professor of medicine at Harvard Medical School and director of the Jiahui International Cancer Center, to share academic topics related to liver cancer immunotherapy
.
The "dumb" organ liver does not release obvious cancer signals.
The treatment of liver cancer encounters challenges.
Professor Zhu Xiuxuan pointed out: "Although there are many treatments for liver cancer patients, some patients can be cured by early liver transplantation or liver ablation, but these treatment methods still have limitations.
sex
.
liver is called 'dumb' organs, liver cancer early no obvious symptoms, the disease has a hidden, rapid progression characteristics, and other symptoms appear, often already belong to the middle and late, which makes many patients missed the best time for treatment
.
this part The intervention of patients with advanced liver cancer mainly relies on drugs.
Even if patients can successfully undergo surgical treatment, they are faced with the dilemma of easy recurrence after surgery.
Further drug intervention is still needed to achieve the goal of remission
.
"At present, the clinical diagnosis and treatment of liver cancer still encounters many challenges.
.
"First, traditional chemotherapy has not shown significant efficacy in the treatment of liver cancer; second, the research process of targeted therapy for liver cancer has gone a lot of detours.
Although targeted drugs such as sorafenib and lenvatinib have been developed, patients have achieved good results.
The benefits are relatively limited; third, the use of targeted drugs may have some side effects that may affect the quality of life of patients
.
"Professor Zhu concluded
.
Therefore, in the field of liver cancer treatment, there is an urgent need to develop some drugs that can benefit liver cancer patients.
At the same time, the drugs developed can extend the patient's benefit time to a greater extent, reduce side effects, and improve the quality of life of patients
.
Immune checkpoint inhibitors undoubtedly provide a new direction for the treatment of liver cancer-immune checkpoint inhibitors represented by PD-1/PD-L1 inhibitors have made breakthroughs in the treatment of advanced liver cancer and become an important treatment method in the field of liver cancer
.
immunotherapy hot debut, "T + A" treatment program very often defeated landmark monotherapy, combination therapy has become a new direction to explore
.
Discussion A teplizumab jointly published last year in the top journal "new England Journal of Medicine" The IMbrave150 study of bevacizumab (T+A) for the first-line treatment of advanced liver cancer has made a major breakthrough, becoming the first "ice-breaking" study that has been proven to be superior to sorafenib [2]
.
Research release screenshot "IMbrave150 study" It is an epoch-making research in the field of liver cancer treatment, and its important significance is mainly reflected in the following aspects: First, the IMbrave150 study proved for the first time that compared with sorafenib, "T+A" can significantly prolong the progression-free survival of patients with advanced liver cancer (PFS) and overall survival (OS)
.
Second, in terms of the mechanism of drug action, the study proved for the first time that when immune checkpoint inhibitors and anti-angiogenesis drugs are used in combination, the two have a synergistic effect and enhance the therapeutic effect; third, this study also gives clinicians tips: The combination therapy model has now become an important method for the first-line treatment of liver cancer, and it also provides a basis for the development of subsequent new combination programs
.
"Professor Zhu said
.
A few days ago, the "Lancet-Oncology" published online the results of the "T+A" vs.
Sorafenib in the treatment of unresectable hepatocellular carcinoma patients' quality of life report [3], further explaining that the treatment plan is improving patients OS and PFS can also improve the quality of life
.
The toxicity of immune checkpoint inhibitors cannot be ignored, and timely and reasonable treatment is "turn the tide".
Although the use of immune checkpoint inhibitors has achieved great success, these drugs are also accompanied by immune-related adverse events (pulmonary nodular interstitial inflammation, interstitial pulmonary nodules, etc.
).
Myocarditis, hypophysitis and immune-related dermatitis, etc.
) may cause irreversible effects on vital organs of the body, and severe cases can be life-threatening
.
Therefore, timely, efficient and reasonable treatment of immune-related adverse events is particularly important to improve the efficacy of immunotherapy
.
Professor Zhu emphasized: "The benefits of liver cancer immunotherapy for clinical work and patients are currently a hot spot of concern
.
As mentioned above, most patients with advanced liver cancer receive immunotherapy well tolerated, but the immune-related side effects caused by such drugs The reaction still cannot be completely avoided
.
The timely recognition, diagnosis and treatment of these side reactions are important links in the clinical treatment process
.
In this regard , the Chinese Society of Clinical Oncology (CSCO) and other professional academic groups have made practical efforts and Action, and formulated key guidelines such as the "2021 CSCO Immune Checkpoint Inhibitors Clinical Application Guidelines" and "2021 CSCO Immune Checkpoint Inhibitors Related Toxicity Management Guidelines".
These guidelines can guide clinicians to pay attention to immune-related adverse events in the future , Its judgment and treatment can be systematic and systematic
.
"When a patient has a serious immune-related adverse event, how to deal with it? In response to this question, Professor Zhu added: “Clinical treatment for these patients needs to be very timely.
Patients should stop the drug for life and start high-dose hormone shock therapy quickly
.
If handled in a timely manner, most patients' immune-related adverse events can be effectively controlled
.
There is still much room for further exploration in the monitoring and handling of immune-related adverse events in the future
.
"Multi-directional exploration, the future of liver cancer immunotherapy can be expected.
Finally, Professor Zhu looked forward: "At present, liver cancer immunotherapy has made major breakthroughs, but there is still a lot of room for improvement
.
At the same time, I also hope to carry out more clinical studies related to liver cancer
.
In terms of research direction, a new type of immune combination therapy program is currently being explored, including small molecule TKI combined immunotherapy, which has now entered clinical phase III research
.
In addition, another direction that is still being explored at this stage is a better treatment plan for patients with early liver cancer.
For example, patients with a high risk of recurrence after surgery should apply effective treatment plans in the early stage of the disease to reduce the risk of tumor recurrence and even achieve cure
.
The development of new immune checkpoint inhibitors, including the exploration of PD-1, PD-L1 and CTLA-4 blockers, is another important direction; CAR-T cell therapy is also under development,” although the therapy The results of the application in liver cancer are still immature, but I also look forward to the progress and results of cell therapy in the field of liver cancer treatment
.
"Expert Profile" Professor Zhu Xiuxuan Professor Andrew X.
Zhu MD, PhD, Harvard Medical School Professor of Medicine, Harvard University Massachusetts General Hospital, former director of the Liver Cancer Research Center, Chief Scientific Officer of Shanghai Jiahui International Hospital and Director of the Jiahui International Cancer Center International Liver Cancer and Authoritative expert on cholangiocarcinoma International Liver Cancer Association (ILCA) Founding Council Member NCCN, AASLD, ASCO Liver Cancer Guidelines Editorial Board ASCO Research Fund Judge, International Cholangio Cancer Foundation Clinical Research Committee Deputy Director CSCO Overseas Expert Committee Deputy Director V Foundation Translational Research Award , Lorenzo-Capussotti Outstanding Contribution Award and Jonathan Kraft Translational Research Award References: [1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F.
Global cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality worldwide for 36 cancers in 185 countries.
CA Cancer J Clin.
2021 Feb 4.
doi:10.
3322/caac.
21660.
[2] Finn RS, Qin S, Ikeda M, et al.
Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma.
N Engl J Med 2020;382:1894-905.
[3]Galle PR, Finn RS, Qin S, Ikeda M, Zhu AX, Kim TY, Kudo M, Breder V, Merle P, Kaseb A, Li D, Mulla S, Verret W, Xu DZ, Hernandez S, Ding B, Liu J, Huang C, Lim HY, Cheng AL, Ducreux M.
Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial.
Lancet Oncol.
2021 May 27:S1470-2045(21)00151-0.
doi: 10.
1016/S1470-2045(21)00151-0.
Epub ahead of print.
PMID: 34051880.
Primary liver cancer is one of the common malignant tumors of the digestive system in China.
Its morbidity and mortality rank 6th among global cancers.
The third place, the main pathological type is hepatocellular carcinoma, accounting for about 85% [1], the overall five-year survival rate of patients with advanced liver cancer is still low
.
At the 7th BiG IMPACT Annual Conference hosted by the BiG Biomedical Innovation Society a few days ago, the "medical community" was fortunate to invite Zhu Xiuxuan, a professor of medicine at Harvard Medical School and director of the Jiahui International Cancer Center, to share academic topics related to liver cancer immunotherapy
.
The "dumb" organ liver does not release obvious cancer signals.
The treatment of liver cancer encounters challenges.
Professor Zhu Xiuxuan pointed out: "Although there are many treatments for liver cancer patients, some patients can be cured by early liver transplantation or liver ablation, but these treatment methods still have limitations.
sex
.
liver is called 'dumb' organs, liver cancer early no obvious symptoms, the disease has a hidden, rapid progression characteristics, and other symptoms appear, often already belong to the middle and late, which makes many patients missed the best time for treatment
.
this part The intervention of patients with advanced liver cancer mainly relies on drugs.
Even if patients can successfully undergo surgical treatment, they are faced with the dilemma of easy recurrence after surgery.
Further drug intervention is still needed to achieve the goal of remission
.
"At present, the clinical diagnosis and treatment of liver cancer still encounters many challenges.
.
"First, traditional chemotherapy has not shown significant efficacy in the treatment of liver cancer; second, the research process of targeted therapy for liver cancer has gone a lot of detours.
Although targeted drugs such as sorafenib and lenvatinib have been developed, patients have achieved good results.
The benefits are relatively limited; third, the use of targeted drugs may have some side effects that may affect the quality of life of patients
.
"Professor Zhu concluded
.
Therefore, in the field of liver cancer treatment, there is an urgent need to develop some drugs that can benefit liver cancer patients.
At the same time, the drugs developed can extend the patient's benefit time to a greater extent, reduce side effects, and improve the quality of life of patients
.
Immune checkpoint inhibitors undoubtedly provide a new direction for the treatment of liver cancer-immune checkpoint inhibitors represented by PD-1/PD-L1 inhibitors have made breakthroughs in the treatment of advanced liver cancer and become an important treatment method in the field of liver cancer
.
immunotherapy hot debut, "T + A" treatment program very often defeated landmark monotherapy, combination therapy has become a new direction to explore
.
Discussion A teplizumab jointly published last year in the top journal "new England Journal of Medicine" The IMbrave150 study of bevacizumab (T+A) for the first-line treatment of advanced liver cancer has made a major breakthrough, becoming the first "ice-breaking" study that has been proven to be superior to sorafenib [2]
.
Research release screenshot "IMbrave150 study" It is an epoch-making research in the field of liver cancer treatment, and its important significance is mainly reflected in the following aspects: First, the IMbrave150 study proved for the first time that compared with sorafenib, "T+A" can significantly prolong the progression-free survival of patients with advanced liver cancer (PFS) and overall survival (OS)
.
Second, in terms of the mechanism of drug action, the study proved for the first time that when immune checkpoint inhibitors and anti-angiogenesis drugs are used in combination, the two have a synergistic effect and enhance the therapeutic effect; third, this study also gives clinicians tips: The combination therapy model has now become an important method for the first-line treatment of liver cancer, and it also provides a basis for the development of subsequent new combination programs
.
"Professor Zhu said
.
A few days ago, the "Lancet-Oncology" published online the results of the "T+A" vs.
Sorafenib in the treatment of unresectable hepatocellular carcinoma patients' quality of life report [3], further explaining that the treatment plan is improving patients OS and PFS can also improve the quality of life
.
The toxicity of immune checkpoint inhibitors cannot be ignored, and timely and reasonable treatment is "turn the tide".
Although the use of immune checkpoint inhibitors has achieved great success, these drugs are also accompanied by immune-related adverse events (pulmonary nodular interstitial inflammation, interstitial pulmonary nodules, etc.
).
Myocarditis, hypophysitis and immune-related dermatitis, etc.
) may cause irreversible effects on vital organs of the body, and severe cases can be life-threatening
.
Therefore, timely, efficient and reasonable treatment of immune-related adverse events is particularly important to improve the efficacy of immunotherapy
.
Professor Zhu emphasized: "The benefits of liver cancer immunotherapy for clinical work and patients are currently a hot spot of concern
.
As mentioned above, most patients with advanced liver cancer receive immunotherapy well tolerated, but the immune-related side effects caused by such drugs The reaction still cannot be completely avoided
.
The timely recognition, diagnosis and treatment of these side reactions are important links in the clinical treatment process
.
In this regard , the Chinese Society of Clinical Oncology (CSCO) and other professional academic groups have made practical efforts and Action, and formulated key guidelines such as the "2021 CSCO Immune Checkpoint Inhibitors Clinical Application Guidelines" and "2021 CSCO Immune Checkpoint Inhibitors Related Toxicity Management Guidelines".
These guidelines can guide clinicians to pay attention to immune-related adverse events in the future , Its judgment and treatment can be systematic and systematic
.
"When a patient has a serious immune-related adverse event, how to deal with it? In response to this question, Professor Zhu added: “Clinical treatment for these patients needs to be very timely.
Patients should stop the drug for life and start high-dose hormone shock therapy quickly
.
If handled in a timely manner, most patients' immune-related adverse events can be effectively controlled
.
There is still much room for further exploration in the monitoring and handling of immune-related adverse events in the future
.
"Multi-directional exploration, the future of liver cancer immunotherapy can be expected.
Finally, Professor Zhu looked forward: "At present, liver cancer immunotherapy has made major breakthroughs, but there is still a lot of room for improvement
.
At the same time, I also hope to carry out more clinical studies related to liver cancer
.
In terms of research direction, a new type of immune combination therapy program is currently being explored, including small molecule TKI combined immunotherapy, which has now entered clinical phase III research
.
In addition, another direction that is still being explored at this stage is a better treatment plan for patients with early liver cancer.
For example, patients with a high risk of recurrence after surgery should apply effective treatment plans in the early stage of the disease to reduce the risk of tumor recurrence and even achieve cure
.
The development of new immune checkpoint inhibitors, including the exploration of PD-1, PD-L1 and CTLA-4 blockers, is another important direction; CAR-T cell therapy is also under development,” although the therapy The results of the application in liver cancer are still immature, but I also look forward to the progress and results of cell therapy in the field of liver cancer treatment
.
"Expert Profile" Professor Zhu Xiuxuan Professor Andrew X.
Zhu MD, PhD, Harvard Medical School Professor of Medicine, Harvard University Massachusetts General Hospital, former director of the Liver Cancer Research Center, Chief Scientific Officer of Shanghai Jiahui International Hospital and Director of the Jiahui International Cancer Center International Liver Cancer and Authoritative expert on cholangiocarcinoma International Liver Cancer Association (ILCA) Founding Council Member NCCN, AASLD, ASCO Liver Cancer Guidelines Editorial Board ASCO Research Fund Judge, International Cholangio Cancer Foundation Clinical Research Committee Deputy Director CSCO Overseas Expert Committee Deputy Director V Foundation Translational Research Award , Lorenzo-Capussotti Outstanding Contribution Award and Jonathan Kraft Translational Research Award References: [1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F.
Global cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality worldwide for 36 cancers in 185 countries.
CA Cancer J Clin.
2021 Feb 4.
doi:10.
3322/caac.
21660.
[2] Finn RS, Qin S, Ikeda M, et al.
Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma.
N Engl J Med 2020;382:1894-905.
[3]Galle PR, Finn RS, Qin S, Ikeda M, Zhu AX, Kim TY, Kudo M, Breder V, Merle P, Kaseb A, Li D, Mulla S, Verret W, Xu DZ, Hernandez S, Ding B, Liu J, Huang C, Lim HY, Cheng AL, Ducreux M.
Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial.
Lancet Oncol.
2021 May 27:S1470-2045(21)00151-0.
doi: 10.
1016/S1470-2045(21)00151-0.
Epub ahead of print.
PMID: 34051880.
