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20 18 Ten Events of Tumor Immunotherapy
Beijing time 65438+1 October1news, 20 18 Nobel Prize in Physiology or Medicine announced!
American scientist James P. Allison and Japanese scientist Tasuku Honjo won the 20 18 Nobel Prize in Physiology or Medicine in recognition of their contribution to "discovering the treatment of cancer through negative immunomodulation".
As many people have said, the pioneering contributions of Professor Allison, Professor Tasuku Honjo and other researchers in immunotherapy have completely changed the mode of human struggle against cancer.
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Why can immunotherapy win the Nobel Prize? You should know these knowledge points.
Immunotherapy has been proved to play an important role in many cancers. Although the antibodies of CTLA4 and PD-L 1/PD- 1 have been successfully tested in clinical trials, only a small number of patients show lasting clinical response, which indicates that a wider understanding of cancer immunity is still needed at this stage.
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Count the "immediate and collateral relatives" of immunotherapy
With the successful listing of Nivolumab approved by the State Administration of Medical Supplies, patients with non-small cell lung cancer (NSCLC) in China ushered in a new era of immunotherapy. Because tumor immunotherapy is a new treatment method, doctors are still troubled by many problems after the advent of clinical drugs. For example, which patients with non-small cell lung cancer are the dominant group in tumor immunotherapy, whether Nivolumab can be used in the first line, whether PD-L 1 should be tested before treatment, how to deal with immune-related adverse reactions and so on. Yimaitong specially invited Professor Cui Jiuyi from the Oncology Department of the Cancer Center of the First Hospital of Jilin University to tell you about the clinical use guidance after the advent of tumor immunotherapy. The following are the details.
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Expert interview with Professor Cui Jiuyi: There are guidelines for clinical use after tumor immunotherapy.
With the introduction of immune checkpoint inhibitors into China, a large number of patients with non-small cell lung cancer (NSCLC) will have the opportunity to receive immunotherapy, so as to get a chance of long-term survival. At present, Nivolumab, the only immune checkpoint inhibitor for non-small cell lung cancer on the market in China, has been approved as a monotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer whose epidermal growth factor receptor (EGFR) gene mutation and anaplastic lymphoblastic enzyme (ALK) are negative, and has received platinum-containing chemotherapy before.
In the indications of SDFA approved in China, no examination is required, such as PD-L 1 or TMB (tumor mutation load). A doctor asked, "Is it necessary to carry out PD-L 1 test on second-line Nivolumab?"
First of all, the origin of the question is: Can immunotherapy find a satisfactory predictor? In the clinical trials of immunotherapy, researchers tried to explore the possible beneficiaries of immunotherapy from a variety of markers. PD-L 1 is a potential predictive marker, but its expression fluctuates greatly, so it is challenging to be a unified predictive marker. Blueprint research tells us that the consistency of detecting the expression level of PD-L 1 between different platforms is not good, and the detection method is still controversial.
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Nivolumab is used to read the second line of IO happily. Is it necessary to test PD-L 1?
On June 15, Nivolumab-Odivo was successfully listed in China, and patients with non-small cell lung cancer (NSCLC) in China finally welcomed tumor immunotherapy drugs. After the advent of immune checkpoint inhibitors, clinicians and patients will no longer face the "cold" clinical trial data, but more and more urgently need to face the real world big data of tumor immunotherapy for non-small cell lung cancer.
In view of the difference between the real world and clinical trials of tumor immunotherapy, and the expectation of the real application of tumor immunotherapy in China non-small cell lung cancer population, Yimaitong specially interviewed Professor Yang Yanji from the Cancer Center of Guangdong Provincial People's Hospital.
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Interview with Professor Yang: Tumor immunotherapy in the real world
Immunotherapy has achieved many curative effects in the field of tumor, which has brought the possibility of long-term survival for a variety of tumor patients. While paying attention to the efficacy of immunotherapy, clinicians and patients also began to pay more attention to immunotherapy-related adverse reactions (irAE). The mechanism of immunotherapy is different from traditional chemotherapy and targeted therapy, so the toxicity of irAE is also different from chemotherapy and targeted therapy. In addition, immunotherapy is a new treatment method, so we should pay attention to the treatment of irAE. Therefore, Yimaitong specially interviewed Professor Zhou Chengzhi from the key points of irAE management, general principles, the treatment of pulmonary toxicity that everyone is most concerned about, and the reuse of immunotherapy after irAE. I hope everyone will be more familiar with the management principles and methods of irAE.
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Expert interview with Professor Zhou Chengzhi: Principles and methods of handling immune-related adverse reactions
For a long time, platinum-based chemotherapy has been the main first-line treatment for patients with non-small cell lung cancer without driver gene mutation, but its effect is limited. Immunotherapy can improve the survival outcome of this group and completely change the treatment prospect, shifting the focus of first-line treatment of non-small cell lung cancer to immunotherapy.
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Single drug or combined drug? This is a problem.
Since the field of tumor therapy entered the era of immunotherapy, a variety of tumor species have blossomed in an all-round way, and patients have benefited from the survival frequently. Nowadays, tumor treatment has gradually entered the era of immunotherapy 2.0. During this period, the focus of clinical research is to determine the people who benefit the most, and to optimize and select the dominant patients. Biomarkers are one of the main means to guide the clinical decision-making of immunotherapy. At present, PD-L 1 and TMB are the main markers for predicting the efficacy of immune checkpoint inhibitors for non-small cell lung cancer. What is the relationship between them and the efficacy of immune checkpoint inhibitors? What are the advantages and disadvantages? Are there any other suitable biomarkers?
Yimaitong invited Professor Wang Jie from Cancer Hospital of China Academy of Medical Sciences to write a paper explaining the biomarkers of immunotherapy for non-small cell lung cancer.
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Professor Wang Jie: Biomarkers of immunotherapy for non-small cell lung cancer from an expert's point of view.
In the 1970s, monoclonal antibodies against specific targets appeared, and then a variety of monoclonal antibodies for tumor treatment appeared, such as immune checkpoint inhibitors. This paper mainly reviews the application of PD- 1 immune checkpoint inhibitors in various tumors.
Monoclonal antibodies play an anti-tumor role mainly by binding with antigens expressed on the surface of tumor cells. The main mechanisms include: a) inducing apoptosis or down-regulating cell survival signal, which directly produces cytotoxicity; B) presenting cytotoxic agents and radiotherapy agents; C) Antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity; D) Targeting growth factors and vascular system, thereby preventing tumor generation; E) targeting the connection of stromal cells or microenvironment.
PD- 1 is an immune checkpoint belonging to CD28/CTLA-4 receptor family, which binds to two known ligands, namely, PD-L 1 and PD-L2. Once PD- 1 binds to PD-L 1, the function of T cells is down-regulated. PD- 1 and PD-L 1 inhibitors can be used to treat various malignant tumors.
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Application of PD- 1 inhibitor in various tumors
At present, immunotherapy is the darling of the tumor community, especially the immune checkpoint inhibitor (ICIs) may be the most promising immunotherapy. Different from chemotherapy and targeted therapy, ICIs directly acts on the autoimmune system, blocking the combination of immune checkpoints (such as PD- 1) and their ligands, restoring the activation and proliferation of T cells, thus killing tumor cells.
Different from traditional treatment methods, its mechanism of action also makes immunotherapy have unique characteristics. It is reflected in the lasting response and long-term survival of curative effect; Unconventional delayed reaction and wrong progress of reaction mode; And because of its unconventional coping style, it may need a new evaluation end point; Finally, in terms of side effects, it also has its own unique immunotherapy-related adverse reactions (irAE).
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This paper reviews the characteristics of tumor immunotherapy.
Immunotherapy is changing the mode of tumor treatment, and some patients have achieved long-term survival and lasting response after immunotherapy; However, immunotherapy not only brings impressive curative effect, but also has side effects. Different from traditional treatment, the side effects associated with immune checkpoint inhibitors are unique, which is called immunotherapy-related adverse reactions (irAE). With the extensive use of immunoscreening inhibitors, irAE has attracted more and more attention. Yimaitong invited Director Rebecca of Cancer Hospital of China Academy of Medical Sciences to answer the common 10 questions in clinical irAE.
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Interview with Professor Rebecca: irAE 10 Q
The central nervous system is a common metastatic site of lung cancer, and 10% patients will appear at the first diagnosis. According to literature statistics, the brain metastasis rate of lung cancer and bronchial cancer is 28% for men and 26% for women. Patients with epidermal growth factor receptor (EGFR) mutation have a higher probability, about 44% (brain metastasis and meningeal metastasis).
The prognosis of patients with brain metastasis from non-small cell lung cancer (NSCLC) is very poor. Without treatment, the average survival time is less than 7 weeks. Although small cell lung cancer only accounts for 15% of lung cancer, its pathological features show that it is highly malignant and easy to metastasize early. About 80% of small cell lung cancer will have brain metastasis during its development, and the median survival time of treated small cell lung cancer is only 5 months.
Before immunotherapy appeared, radiotherapy was the main treatment for brain metastases. Stereotactic radiotherapy), surgery, chemotherapy and targeted therapy. With the development of diagnosis and treatment technology, the survival time of patients with brain metastases has been prolonged, but the treatment needs of patients have not been met.
With the development of immune checkpoint inhibitors (ICI), a new approach has been opened up for the treatment of lung cancer, especially non-small cell lung cancer.
Brain metastasis can be regarded as the back garden of lung cancer. Facing the heavy curtain and heavy cymbals, let's take a look at how immunotherapy works, offering flowers and offering sacrifices to snow and forbearing to enter the harem.
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Progress in immunotherapy for brain metastases from lung cancer
Compared with patients with non-small cell lung cancer under 65 years old, the morbidity and mortality of elderly patients have increased exponentially. According to statistics, the median age of onset and death of non-small cell lung cancer is 70 and 72 years respectively. Can elderly patients also benefit from immunotherapy as immune checkpoint inhibitors change the treatment mode of non-small cell lung cancer?
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Application of immune checkpoint inhibitors in elderly patients with non-small cell lung cancer: advantages or disadvantages?
At present, the drug approved by NMPA for immunotherapy of lung cancer (especially the immune checkpoint inhibitor here) is nivolumab (? ), the indications are: single-drug therapy for adult patients with locally advanced or metastatic non-small cell lung cancer (non-small cell lung cancer) who have mutation of epidermal growth factor receptor (EGFR) gene and negative anaplastic lymphoblastic enzyme (ALK) and have received platinum-containing chemotherapy in the past.
Based on the evidence of clinical studies, three large-scale phase III studies (CheckMate 0 17/057/078) established a new high level of second-line treatment of Nivolumab. However, in clinical practice, the second-line regimen of some patients is not docetaxel alone. If chemotherapy+anti-angiogenesis therapy is selected as the control scheme, which is better, Nivolumab vs chemotherapy+anti-angiogenesis therapy? This is a concern of clinicians. If there is no evidence to support it, we really can't jump to conclusions! Mmetagazine, a scientific report from June 2065438 to June 2008, published an indirect comparative meta-analysis to answer this question.
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Second-line treatment of advanced non-small cell lung cancer: immunotherapy vs chemotherapy+anti-angiogenesis, which is better?