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2018 Top 10 Events in Tumor Immunotherapy
On October 1, Beijing time, the 2018 Nobel Prize in Physiology or Medicine was announced!
American scientist James P. Allison and Japanese scientist Tasuku Honjo have been awarded the 2018 Nobel Prize in Physiology or Medicine for their contributions to the "discovery of therapies for the treatment of cancer with negative immune modulation".
As many have said, the pioneering contributions of Prof. Allison and Prof. Honjo, as well as other researchers, to immunotherapy have revolutionized the landscape of humanity's fight against cancer.
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Why did immunotherapy win the Nobel Prize? Here's what you need to know
Immunotherapy has been shown to have important anti-tumor effects in a variety of cancers, and although CTLA4 and PD-L1/PD-1 antibodies have been successful in clinical trials, only a small percentage of patients have shown durable clinical responses, suggesting that a broader understanding of cancer immunity is still needed at this stage.
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Immunotherapy's "immediate and extended family members"
With the successful launch of natalizumab through the approval of the State Drug Administration (SDA), a new era of immunotherapy has been ushered in for Chinese patients with non-small cell lung cancer (NSCLC). Since tumor immunotherapy is an emerging treatment, doctors are still plagued by many problems after the clinical drug is available. For example, which NSCLC patients are the advantageous population for tumor immunotherapy, whether nabulizumab can be used in the first line, whether PD-L1 should be tested before treatment or not, how to deal with immune-related adverse reactions, and so on. Medical Pulse has invited Professor Cui Jiushiwei from the Department of Oncology, Oncology Center of the First Hospital of Jilin University to talk about the clinical use of tumor immunotherapy accessible guidance, the following are the details.
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Expert interview丨Professor Cui Jiowei: Clinical use of tumor immunotherapy after accessibility
Immuno-checkpoint inhibitors have entered China, and a large number of patients with non-small-cell lung cancer (NSCLC) will have the opportunity to undergo immunotherapy to obtain a chance of long-term survival. Navulizumab, the only immune checkpoint inhibitor for NSCLC currently available in China, is approved for the treatment of patients with EGFR-negative and ALK-negative NSCLC who have previously received platinum-based chemotherapy and have progressed or are intolerant of locally advanced or refractory NSCLC. intolerable adult patients with locally advanced or metastatic NSCLC.
The approved indications for SDFA in China do not specify any testing such as PD-L1 or TMB (tumor mutation load). A doctor asked, "Is PD-L1 testing required for second-line use of navulizumab?"
First, the question originates: can immunotherapy find satisfactory predictive markers? In clinical trials of immunotherapy, researchers try to explore the possible beneficiary population of immunotherapy from a variety of markers.PD-L1 is a potential predictive marker, but its expression is volatile and challenging to use as a uniform predictive marker.The Blueprint study tells us that the consistency of detecting PD-L1 expression levels between different platforms is poor, and the assay methodology is still highly The Blueprint study tells us that there is poor consistency in detecting PD-L1 expression levels across platforms, and the assay methodology is controversial.
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Yue Ran Read IO second-line use of nabulizumab, whether PD-L1 testing is required
On June 15, nabulizumab-ODIVA was successfully approved for marketing in China, and patients with non-small-cell lung cancer (NSCLC) in China finally welcomed a tumor immunotherapy drug. With the availability of immune checkpoint inhibitors, clinicians and patients will no longer be faced with "cold" clinical trial data, but more and more urgently with the need to face the real-world data of tumor immunotherapy for NSCLC.
In response to the differences between the real world of tumor immunotherapy and clinical trials, as well as the expectations for the real-world application of tumor immunotherapy in China's NSCLC population, MediPulse interviewed Prof. Dicky Yang from the Oncology Center of Guangdong Provincial People's Hospital.
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Expert Interview 丨Professor Yang: NSCLC Tumor Immunotherapy in the Real World
Immunotherapy has achieved remarkable efficacy in the field of oncology, and has made long-term survival possible for many types of patients with tumors. While focusing on the efficacy of immunotherapy, clinicians and patients have begun to pay more attention to immunotherapy-associated adverse events (irAE). The mechanism of action of immunotherapy is different from that of traditional chemotherapy and targeted therapy, so the toxicity of irAE is also different from that of chemotherapy and targeted therapy. In addition, immunotherapy is a novel therapeutic approach, so the management of irAE may deserve more attention. Therefore, Medical Pulse interviewed Professor Zhou Chengzhi of the First Affiliated Hospital of Guangzhou Medical University from the key points of management of irAE, general principles, and management of pulmonary toxicity, which is the most concerned point, as well as the reuse of immunotherapy after the occurrence of irAE in the hope that we can further familiarize ourselves with the principles and methods of the management of irAE.
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Expert Interview 丨Professor Zhou Chengzhi: Principles and Methods of Managing Immunity-Related Adverse Events (irAE)
Platinum-based chemotherapy has long been the primary first-line treatment option for patients with non-small-cell lung cancer without a driver mutation, but has had limited success. Immunotherapy can improve survival outcomes in this population and is revolutionizing the treatment landscape, shifting the focus of first-line therapy for NSCLC to immune-combination therapy.
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Single agent or combination? That is the question
Since the era of immunotherapy, the field of tumor treatment has seen a full blossoming of multi-tumor species and frequent reports of patient survival benefits. Nowadays, oncology treatment is gradually moving into the immunotherapy 2.0 era, in which clinical research focuses on defining the population with the greatest benefit, optimizing and selecting advantageous patients. Biomarkers are one of the main tools to guide clinical decisions in immunotherapy. Currently, PD-L1 and TMB are the main biomarkers used to predict the efficacy of immune checkpoint inhibitors in NSCLC; how do they relate to the efficacy of immune checkpoint inhibitors? What are their advantages and disadvantages? Are there other suitable biomarkers?
MediPulse has invited Prof. Wang Jie from the Cancer Hospital of the Chinese Academy of Medical Sciences to write an article to explain the biomarkers for immunotherapy of non-small cell lung cancer.
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Expert's Perspective 丨Professor Wang Jie: Biomarkers for Immunotherapy of Non-Small-Cell Lung Cancer
In the 1970s, monoclonal antibodies targeting specific targets were introduced, and since then a number of monoclonal antibodies have emerged as monoclonal antibodies used in tumor therapy, such as immune checkpoint inhibitors. This article focuses on the application of PD-1 immune checkpoint inhibitors in various tumors.
Monoclonal antibodies produce anti-tumor effects mainly by binding to antigens expressed on the surface of tumor cells, and the main mechanisms include: a) direct cytotoxicity by inducing apoptosis or down-regulation of cell survival signals, b) presentation of cytotoxic and radiotherapeutic agents, c) antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, d) targeting of growth factors and vasculature system, thereby preventing tumorigenesis, and e) targeting stromal cells or microenvironmental junctions.
PD-1 is an immune checkpoint belonging to the CD28/CTLA-4 receptor family that binds to two known ligands, PD-L1 and PD-L2.PD-1 down-regulates T-cell function once it binds to PD-L1.PD-1 and PD-L1 inhibitors are used in the treatment of various malignancies.
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An article reading丨PD-1 inhibitors in a variety of tumors
Nowadays, immunotherapy can be considered the darling of the tumor community, especially immune checkpoint inhibitors (ICIs) may be the most promising immune therapy.ICIs, unlike chemotherapy and targeted therapies that act on tumor cells, are directly act on the autoimmune system, blocking immune checkpoints (e.g. PD-1) from binding to their ligands, and restoring T-cell activation and proliferation to kill tumor cells.
The mechanism of action is different from that of traditional treatment, which gives immunotherapy its unique characteristics. In terms of efficacy, there are durable responses and long-term survival; in terms of response patterns, there are unconventional delayed responses and pseudoprogression; and because of its unconventional response patterns, new endpoints may be required for evaluation; and finally, in terms of toxicity, there are unique immunotherapy-associated adverse events (irAEs).
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An overview of the characteristics of tumor immunotherapy
Immunotherapy is changing the landscape of tumor treatment, with some patients achieving long-term survival and durable responses after immunotherapy; however, while immunotherapy offers impressive efficacy, it can also have toxic side effects. Unlike conventional treatments, the side effects associated with immune checkpoint inhibitors are unique and are called immunotherapy-associated adverse effects (irAE). As the application of immune checkpoint inhibitors increases, people are more concerned about irAE. MediPulse has invited Wang Yan, director of the Cancer Hospital of the Chinese Academy of Medical Sciences, to answer 10 common questions about clinical irAE.
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Expert Interview丨Professor Wang Yan: 10 Questions on irAE
The central nervous system is a common site of metastasis for lung cancer, which is present in 10% of patients at the time of their initial consultation; according to literature, the brain metastasis rate of lung and bronchus cancers is 28% in men and 26% in women; the rate of brain metastasis in patients with epidermal growth factor receptor ( EGFR) mutations have a higher probability of occurrence, approximately 44% (brain and meningeal metastases).
Patients with brain metastases from non-small cell lung cancer (NSCLC) have an extremely poor prognosis, with a mean median survival time of less than 7 weeks in the absence of treatment. Although small cell lung cancer (SCLC) accounts for only 15% of lung cancers, the pathologic features show high malignancy and are more prone to early metastasis. About 80% of SCLC will develop brain metastasis in the course of development, and the median survival time of treated SCLC is only 5 months.
Before the emergence of immunotherapy, brain metastases were mainly treated with radiotherapy (whole brain radiotherapy & stereotactic radiotherapy), surgery, chemotherapy and targeted therapy. With the development of diagnostic and therapeutic technology, the OS of brain metastasis patients has been prolonged, but the treatment needs of patients are still unmet.
With the development of Immuno-Checkpoint Inhibitor (ICI ), it opens a new way for the treatment of lung cancer, especially NSCLC.
Brain metastasis can be regarded as the backyard palace of lung cancer. In the face of the heavy mantle and thick door, let's see how immunotherapy pulls out the hairpin and picks the lamp, flicks the flower and sacrifices the snow, and moves the heart and patience, and enters the backyard palace.
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V Spice has the goods | Immunotherapy progress in lung cancer brain metastasis
Compared with NSCLC patients under 65 years of age, the morbidity and mortality rates of elderly patients have increased exponentially. Statistically, the median age of morbidity and mortality in NSCLC is 70 and 72 years. With immune checkpoint inhibitors changing the treatment landscape for NSCLC, could older patients also benefit from immunotherapy?
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YUE RAN READING IO | Immune checkpoint inhibitors in elderly NSCLC patients: advantage or disadvantage?
The current NMPA-approved drug for immunotherapy (specifically immune checkpoint inhibitors in this case) for lung cancer is nabulizumab (nivolumab, OuDivo?).
Based on clinical research evidence, 3 large phase III studies (CheckMate 017/057/078) established nabulizumab as the new height of second-line therapy. However, in clinical practice, there are some patients whose second-line regimen is not docetaxel monotherapy. If the control regimen is chemotherapy + anti-angiogenic therapy, then nabulizumab vs chemotherapy + anti-angiogenic therapy, which is better? This is a question of concern for clinicians, and one really can't jump to conclusions if there is no evidence to support it.A meta-analysis of indirect comparisons published in the June 2018 Scientific Reports journal answers this question.
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Yue Ran Read IO | Second-line treatment for advanced NSCLC: Immunization monotherapy vs chemotherapy + anti-angiogenesis, which is better?