NSCLC's front -line "de -chemotherapy" Chinese research shines 2022 ESMO, starts the new mode of "immunity+"

*For medical professionals for reading reference

Immunomorphic combination of anti -vascular production drugs "combined fist" to break the traditional treatment pattern.

The annual global tumor industry event-the European Cancer Internal Science Association (ESMO) conference was held in Paris, France in September. A SUNRISE study led by Professor Han Baohui, an affiliated to the School of Medicine, Shanghai Jiaotong University, was selected as an oral report of ESMO conference. ) Random and control research [1], "Medical" invites Professor Han Baohui to share the relevant opinions on the research.

Immune+anti -vascular combination,

Phase I study shows its encouraging effect

In recent years, the treatment of lung cancer has progressed rapidly, and the treatment methods such as immunotherapy and antiovascular generation treatment have emerged endlessly. The growth and metastasis of tumors depends on the formation of tumor new blood vessels. The treatment of anti -vascular production has gradually attracted people's attention. However, patients receiving antibody generating single drug treatment have not been obviously improved. [2] With the approval of related drugs such as PD-1 monoclonal anti-anti-resistance and PD-L1 monoclonal anti-resistance, immune examination point inhibitors have become a research hotspot in the field of lung cancer, which greatly improves the prognosis of some patients with lung cancer, but the treatment of immunogenic drugs The mode is only applicable to PD-L1 high-expression population. How to expand immunotherapy response people is currently urgent issues [3].

Antiovascular generating drugs combined with immunotherapy can theoretically improve the efficacy of immunotherapy [4]. Preclinical studies have confirmed that immunotherapy and antiovascular generation drugs are combined to have synergistic efficiency and efficiency. Strong combination effect [5]. Professor Han Baohui pointed out that in Phase I in the past [6], Schidi Midella and Arotinib showed inspiring effects in the advanced NSCLC of the first -line therapy to drive gene negative. This study was included in 22 patients with IIIB/C or IV -stage NSCLC patients who have not been treated and do not have an EGFR/ALK/ROS1 mutation. The disease control rate (DCR) is 100 %, and the median without progress (PFS) is 15 months. The study also observed that regardless of the expression of PD-L1, tumor mutation load (TMB) height, all patients can benefit from combined therapy and have good tolerance.

The preliminary results of Sunrise research are remarkable,

The effect is lasting, safe and tolerant

Under the encouragement of this phase Ⅰ research result, in order to further explore the efficacy and safety of the first -line therapy NSCLC in the first -line therapy of the Cyli Mippitum to achieve the purpose of "de -chemotherapy" in clinical treatment, Professor Han Baohui team launched it. Cindy Metico's SUNRISE Study of the Standard Chemotherapy with Aerotinib compared to standard chemotherapy [1]. Professor Han Baohui said that Sunrise is a phase II study that is open, multi -center, and random, and is included in Phase IV, unbustly, EGFR/ALK/ROS1 -negative NSCLC patients. In terms of admission patients, at the same time, patients with squamous and non-squamous carcinoma were included, and patients with brain metastases and patients with liver metastases were also included. The median age was 64-65 years old. Patients in the group are randomly allocated at 1: 1 to the Cyli Metico combined with the Arotinib group or the platinum -containing chemotherapy group. The patients of the chemotherapy group were allowed to cross to Nobeli Midurate treatment after the disease progressed, and for the patient to obtain the opportunity of backline immunotherapy [1].

Figure 1.Sunrise research design

As of July 15, 2022, 40 patients in 40 patients in the Better Midticope and 43 patients in the chemotherapy group could evaluate the efficacy. The ORR of the Xinyi Mipido and the ORR of the Arotinib group reached 50%, and the ORR of the chemotherapy group was 32.6%. Regardless of the expression of the PD-L1, the Xinyi Metico combined with the Arotinib group was beneficial. Figure 2. The tumor relief situation of the Condi Mipido combined with the Arotinib group and the platinum -containing chemotherapy group

The mid -range relief duration (DOR) of the Xinyi Mipido and the chemotherapy group was 16.3 months and 6.2 months, respectively, and the median PFS was 10.8 months and 5.7 months, respectively. The risk ratio (HR ) It is 0.4, indicating that the risk of disease progress drops by 60%, P = 0.002 [1].

Figure 3. The median DOR and median PFS of the Xindi Mujie Antominib group and the platinum -containing chemotherapy group

In terms of security, the incidence of adverse reactions (Trams) in the treatment of the treatment of Xindi Metrick and the chemotherapy group is 74.4%and 87%, respectively. And 43.5%. Two patients with chemotherapy stopped drugs due to Trams and 1 case of TRAE died. Cindei Mippitum and Aurotinib did not have related events, and the overall security can be tolerated [1].

Table 1. Summary of safety

Professor Han Baohui believes that Sunrise has brought us a new idea- "de -chemotherapy" model. Compared with traditional chemotherapy, immunotherapy has a variety of advantages such as durable response, high cure rate, small toxic and side reactions, and high quality of life of patients. However, the treatment of immunohist medicines is limited, and not all NSCLC patients can benefit from immunotherapy. The audience is only about 30%[7], and the guidelines are given first-line therapy for PD-L1 ≥ 50%of advanced NSCLC patients [8]. Although the treatment of immune+chemotherapy is not affected by the expression of PD-L1, the adverse reactions brought by chemotherapy are greater. Both doctors and patients hope to have the "Chemo-Free" scheme to choose from. SUNRISE research suggests that regardless of the expression of PD-L1, patients who are older and poorly score, cannot tolerate chemotherapy or have worries about chemotherapy, if the gene is negative medical treatement. Compared with chemotherapy, Civy Metrick combined with Aerotinib first -line therapy for NSCLC has a higher effect, longer median PFS, and good security. It is expected that the final result of Sunrise research can bring more guiding significance to the current clinical practice and make more contributions to the treatment of patients with advanced NSCLC.

Immunotherapy is precise and long -term, far away,

The "de -chemotherapy" mode still needs to continue to explore

The "de -chemotherapy" mode of immunomorphic combination of antibodium generating therapy is one of the important diagnosis and treatment strategies in the future. Studies have confirmed that the treatment of antibody production is closely related to the immune microe environment, but not each immunochemical combined antibrokers' treatment plan can allow patients to get patients to obtain patients beneficial. Professor Han Baohui gave an example of another III LEAP-007 study for another immunoaged combined anti-vascular generation treatment plan [9]. The clinical ending of the comparison of immune combined placebo therapy, the total survival period (OS) is negative result. The treatment mode of immune combined antibodium -generating drugs is not only a simple superposition of two drugs, but also whether the unique combination of drugs can bring better treatment effects, how to achieve the effect of the effect and toxic and side reactions in the combined mode and the side reaction of the toxic and side of the side Balance, these are worth reflecting.

In addition, the relationship between tumor blood vessel production and body immune response and changes in the environmental changes in the tumor also requires a more systematic evaluation method to accurately locate the people. How to choose the advantages of combined treatment schemes through reliable biomarkers, how to choose the types of antibodium generating drugs and immunotherapy drugs, determine the cycle and order of the medication, how to adjust the dose of the drug, and at the same time, the safety of combined medication and other issues need to be in the use of medication. Future exploration and resolution.

Expert Introduction

Professor Han Baohui

Shanghai Cheung Hospital

Professor, doctoral supervisor, Honorary Director of Respiratory Medicine

Shanghai leader and excellent discipline leader

Executive Dean of the Chinese Academy of Lunga Cancer

CSCO tumor vascular targeting committee former chairman

Deputy Chairman of the China Anti -Cancer Association Cancer Precision Diagnosis and Treatment Committee

Chairman of the Asia -Pacific Medical Biological Immunization Society of Cancer Branch

Vice Chairman of the Shanghai Anti -Cancer Association (Eighth)

Deputy Chairman of the Shanghai Medical Association Tumor Target Molecular Special Committee, later chairman

Vice President of the Shanghai Physician Society Breathing Society

Good at the diagnosis of lung cancer and multi -disciplinary treatment, lung cancer biological immune targeted therapy and new anti -tumor clinical research. In 2014, he won the second prize of China Medical Science and Technology, the winner of the 8th China Breath Physician Award; and won the Shanghai Medical Science and Technology Award of the second and third prizes. Published more than 300 articles in the field of lung cancer, and led the "Guidelines for the Diagnosis and Treatment of Lung Cancer" of the Chinese Medical Association "Tumor Objective Treatment of Tumor Bio -immune" and "Ultrasonic bronchial mirror technology" monographs, and the main translation "Anti -Tumor Newborn Vascular Treatment".

references:

[1]Baohui Han,Tianqing Chu,Zhuang Yu,et al.Sintilimab plus anlotinib versus platinum-based chemotherapy as first-line therapy in metastatic NSCLC(SUNRISE):an open label,multi-center,randomized,phase 2 study.2022ESMO . [2] Wang Jingyi, Peng Wenying, Jiang Meilin, Wu Lin. The research progress of advanced non -small cell lung cancer in the treatment of advanced non -small cell lung cancer in the treatment of advanced immune examination points in the anti -vascular production drug [J]. Chinese lung cancer magazine, 2021,24 (3): 196-203.

[3]Remon J,Passiglia F,Ahn MJ,et al.Immune Checkpoint Inhibitors in Thoracic Malignancies:Review of the Existing Evidence by an IASLC Expert Panel and Recommendations.J Thorac Oncol.2020;15(6):914-947.

[4] Peng Minhua, Chen Gongxuan. Antharmaceutical therapy and immunotherapy combined with the development of advanced non-small cell lung cancer in the treatment of advanced periods of non-small cell lung cancer [J]. Shandong Pharmaceutical, 2022,62 (17): 85-88.

[5]Manegold C,Dingemans A M C,Gray J E,et al.The potential of combined immunotherapy and antiangiogenesis for the synergistic treatment of advanced NSCLC[J].Journal of Thoracic Oncology,2017,12(2):194-207.

[6] Chu T, zhong R, zhong H, et al.Phase 1B Study of Sintilimab Plus Anlotinib as FIRST-LIRAPY in Patients with Advanced NSCLC.J Thorac Oncol.2021; 16 (4): 643-652.

[7] Zhao Sha, Jiang Tao, Zhou Cai, Anti-PD-1/PD-L1 Immunotherapy Prediction Forecasting Symatic Progress in non-small cell lung cancer [J]. Tumor, 2016,7: 823-828.

[8] NCCN Clinical Practice Guidelines in OnCology: Non-Small Cell LUNG CANCER (Version 4.2022)

[9] T.CSOSZI, J.C.yang, A.LUFT, ET Al.pembrolizumab (PEMBRO) with or Without Lenvatinib (Lenva) in FIRST-LINE METASTATASTASCLC With PD-L1 TPS ≥1%(Leap-007): A PHASE 3, randomized, double-black study.2021 esmo abstract 120o.

*This article is only used to provide scientific information to medical people, and does not represent the viewpoint of this platform

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