Professor Cheng Ying's in-depth interpretation: the advanced way of small cell lung cancer treatment.

With the rapid development of technology and the continuous emergence of new drugs, SCLC treatment will also usher in rapid progress.1. Looking back on the nearly 40 years' journey of small cell lung cancer (SCLC), we have experienced ups and downs along the way, and numerous new drugs have failed to challenge SCLC. How do you feel about this? Why is it so difficult to develop new SCLC drugs? Before immunotherapy, the progress of SCLC was very slow and difficult.since EP (cisplatin combined with etoposide) became the standard treatment option for extensive SCLC in 1985, topotecan has become the only second-line treatment option approved so far in 1996, and few new drugs have been approved for decades.researchers have been exploring therapeutic options that can bring more survival benefits and safety to SCLC.compared with EP regimen, carboplatin combined with etoposide has similar curative effect; except hematological toxicity and other toxicity, irinotecan combined with etoposide has no consistent results compared with EP regimen, and has not been approved by FDA.China has also carried out its own exploration in the first-line treatment of extensive SCLC.the non inferiority phase III study of amlodicin combined with cisplatin (AP) compared with EP regimen showed that the efficacy of AP regimen was similar to that of EP regimen, but AP regimen was not approved due to severe hematologic toxicity.another non inferiority study we conducted was the phase III study of lobaplatin combined with etoposide (LP) compared with EP. It was found that the efficacy of LP was similar to that of EP, and LP regimen was superior to EP in terms of nephrotoxicity, neurotoxicity and gastrointestinal toxicity.according to the results of this study, the Chinese society of Clinical Oncology (CSCO) SCLC guidelines listed LP as an optional strategy for extensive SCLC (2a evidence), and LP regimen became an optional strategy for first-line treatment of extensive SCLC in China.the treatment of recurrent SCLC has not stopped, including the third generation chemotherapy drugs paclitaxel, gemcitabine, docetaxel and a variety of targeted drugs, but failed to surpass topotecan.although the standard of three-line treatment for SCLC has been established, the objective response rate (ORR) is very limited.China's self-developed multi-target small molecule antiangiogenic drug, has improved progression free survival (PFS) and overall survival (OS) in phase II studies of third-line and above SCLC compared with placebo. It has become the first third-line treatment option for SCLC in China approved by the National Drug Administration (nmpa) and written into CSCO guidelines.however, due to the complexity of SCLC genome, it is often the abnormality of transcription factors involved in multiple signaling pathways, the change of gene copy number or epigenetic abnormality. Moreover, the heterogeneity of tumor is significant, especially in relapsed and drug-resistant SCLC. In this case, drugs targeting only one pathway or gene change are difficult to play a role.in addition, the understanding of the origin and pathogenesis of SCLC is still very limited.although the molecular typing of SCLC appears initially, the key defect points and targeted treatment of each subtype have not been determined, and the classification and treatment have not been achieved yet.with the progress of technology and the discovery of new drugs, SCLC will also usher in rapid progress. In the field of non-small cell lung cancer (NSCLC), targeted drugs, anti angiogenesis drugs and immune drugs have achieved good results.compared with this, the progress of SCLC will be "eclipsed".until the last two years, immunotherapy began to emerge in SCLC, and impower 133 research is a good example.in February this year, China's nmpa officially approved the use of atilizumab in combination with chemotherapy for the first-line treatment of extensive SCLC, which is also the first indication of atilizumab approved in China.with the approval of atilizumab, what do you think is the significance of impower 133 research in promoting the therapeutic course and pattern of SCLC? Compared with chemotherapy, atilizumab combined with standard chemotherapy in impower133 study of Professor Cheng Ying prolonged OS of first-line treatment of extensive stage SCLC by 2 months and reduced the risk of death by 30%. It is the first phase III study to improve survival in the first-line treatment of extensive stage SCLC in recent 30 years. It has become a milestone event in the treatment history of SCLC, and also makes immunochemotherapy the first-line treatment of extensive stage SCLC The new standard of treatment.China also contributed 100 patients to the impower 133 study.within less than one year after FDA approval, nmpa approved atilizumab combined with chemotherapy for the first-line treatment of extensive SCLC. Immunotherapy has also become a treatment option for SCLC in China.the research on power imlc has changed the research status and increased the enthusiasm of research.at present, there are five confirmatory phase III studies of extensive stage SCLC first-line immunotherapy in China.in addition, new first-line models are also being explored, including a phase III study on the first-line treatment of extensive SCLC with immunotherapy and anti angiogenesis drugs on the basis of chemotherapy, hoping to double regulate the immune microenvironment of SCLC to further increase the therapeutic effect.in addition, the treatment mode of dual immune combined chemotherapy is also being explored, for example, the treatment mode of tigit inhibitor tiragolumab + atilizumab combined with chemotherapy has entered phase III clinical research.the success of immunotherapy in extensive SCLC also promotes the exploration of immunotherapy combined with chemoradiotherapy in limited phase SCLC.Adriatic study is an international multi center phase III study on consolidation therapy of SCLC after radiotherapy and chemotherapy.in addition, Roche will carry out a phase II Limited phase SCLC with concurrent or sequential chemoradiotherapy to start the study of immunotherapy with atilizumab, and the immunotherapy of domestic immunosuppressive checkpoint inhibitors in limited phase SCLC will also be started.these studies will explain how immunotherapy for limited phase SCLC will be more effective and safer, and may become the basis for changing the therapeutic pattern of limited SCLC in the future. With the development of immunotherapy in SCLC, what problems should be solved in the future (such as biomarker, immunotherapy combined with other therapies)? What other comprehensive treatment methods can be used to further improve the survival time and quality of life of patients with SCLC? Although Professor Cheng Ying has established a new therapeutic pattern of SCLC, only part of SCLC can benefit from immunotherapy, and the survival improvement brought by immunotherapy is still limited.in order to make immunotherapy play a better role in SCLC, it is urgent to clarify the markers of SCLC immunotherapy and the ideal strategy of SCLC immunotherapy.the selection of biomarkers has always been a difficult problem in immunotherapy, and SCLC is no exception.at present, the markers explored by SCLC include PD-L1 expression, tumor mutation load (TMB), tumor immunophenotype and expression profile of inflammation related genes. However, different drugs have tried different markers in SCLC, and the research results are also different. In addition, the selection of markers for immunotherapy in SCLC is consistent with that of other solid tumors, which may require comprehensive evaluation of multiple indicators The selection of biomarkers should be based on a deep understanding of the immune microenvironment and immune escape mechanism of SCLC. studies have found that compared with NSCLC, there are fewer tumor infiltrating lymphocytes in SCLC, especially CD8 + T cells, and the proportion of CD8 + / CD3 + in SCLC is also significantly reduced, suggesting that SCLC is an "immune cold tumor". SCLC has relatively high TMB, but the immunogenicity of new antigens produced by different mutation types is different. SCLC may lack of effective tumor new antigen. In addition, SCLC also has abnormal antigen presenting function. Therefore, combined immunotherapy is a more promising treatment strategy in SCLC. at present, there are two levels of immune combination strategy in SCLC: on the one hand, it can improve the immune microenvironment of SCLC and avoid immune escape through a variety of mechanisms, such as combined chemotherapy, radiotherapy, antiangiogenic drugs, DDR inhibitors, etc. immune combined with multi-target antiangiogenic drugs showed good safety in the preliminary results of phase I study, and the SCLC patients included in the study also achieved good curative effect; on the basis of phase I study, the phase III study of immune combined with multi-target anti angiogenesis drugs plus first-line standard chemotherapy is also in full swing, and it is expected that this new combined treatment mode can be widely used Extensive SCLC brings more survival improvement. on the other hand, the combination of drugs for immune microenvironment or immune regulation, such as OX40 agonist, tigit inhibitor and LAG-3 inhibitor, is also a strategy to improve the survival of SCLC patients. Introduction to experts: Professor Cheng Ying, second-class Professor, doctoral supervisor, enjoying the special allowance of the State Council, young and middle-aged experts with outstanding contributions from the Ministry of health. president of Jilin Cancer Hospital, director of Jilin Cancer Institute, director of Jilin cancer center, director of Jilin Cancer Association Council, director of Jilin lung cancer diagnosis and treatment center, and China Society of Clinical Oncology (CSCO) Vice chairman, chairman of CSCO small cell lung cancer professional committee, vice chairman of CSCO non-small cell lung cancer professional committee, vice chairman of CSCO liver cancer expert committee, vice chairman of CSCO tumor big data expert committee, vice chairman of lung cancer Professional Committee of China Anti Cancer Association, vice chairman of cancer clinical chemotherapy Professional Committee of China Anti Cancer Association, and Chinese medicine He is a member of the oncology branch of the society, vice chairman of the professional editing Committee for regular assessment of oncologists, member of the expert group for standardized diagnosis and treatment of common tumors of the national health and Family Planning Commission, vice chairman of the lung cancer training professional committee of the Chinese Medical Association, chairman of the oncologist branch of the Jilin Medical Association, and chairman of the cancer Professional Committee of the Jilin Medical Association Editorial board member of Chinese Journal of oncology and other journals. "School of immunotherapy for small cell lung cancer" is an academic column in the field of cancer created by the medical community, which delivers a high-quality professional article online every week. to provide doctors and patients with timely and effective information on immunotherapy and the latest clinical progress. the first phase of the wonderful review of the past, the school of immunotherapy for small cell lung cancer was officially launched! Here is the progress and hope that both doctors and patients want to know The second phase, the change of small cell lung cancer treatment: the rise after decades of silence; the third phase: written after the first-line treatment of es-sclc approved by China food and drug administration, phase IV: who will become the star of hope? Does es-sclc immunotherapy need biomarkers detection? The sixth stage | small cell lung cancer treatment can not only "three board axe", these methods understand? Phase 7 | immunization + chemotherapy