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Genomic correlates of the response to first-line PD-1 blockade plus chemotherapy in patients with advanced non-small-cell lung cancer

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中华医学杂志(英文版) 2024年第18期137卷 2024 Aug 21页

作者： Jiang Tao Chen Jian Wang Haowei Wu Fengying Chen Xiaoxia Su Chunxia Zhang Haiping zhou Fei Yang Ying Zhang Jiao Sun Huaibo Zhang Henghui zhou caicun Ren Shengxiang Department of Medical Oncology Shanghai Pulmonary Hospital &amp Thoracic Cancer Institute Tongji University School of Medicine Shanghai China Department of Thoracic Surgery Shanghai Pulmonary Hospital &amp Genecast Biotechnology Co. Ltd Wuxi Jiangsu China Biomedical Innovation Center Beijing Shijitan Hospital Capital Medical University Beijing China School of Oncology Capital Medical University Beijing China

Background: Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced ***: We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort (n = 125), a validation cohort (n = 82), and a control cohort (n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas ***: A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor ***: These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus ch

关键词： Non-small-cell lung cancer (NSCLC) Programmed death 1 (PD-1) blockade Gene panel Prediction Biomarker

The cutting-edge progress of immune-checkpoint blockade in lung cancer

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Cellular & Molecular Immunology 2021年第2期18卷 279-293页

作者： Fei zhou Meng Qiao caicun zhou Department of Medical Oncology Shanghai Pulmonary HospitalThoracic Cancer InstituteTongji University School of MedicineShanghaiChina

Great advances in immune checkpoint blockade have resulted in a paradigm shift in patients with lung ***-checkpoint inhibitor(ICI)treatment,either as monotherapy or combination therapy,has been established as the standard of care for patients with locally advanced/metastatic non-small cell lung cancer without EGFR/ALK alterations or extensive-stage small cell lung *** increasing number of clinical trials are also ongoing to further investigate the role of ICIs in patients with early-stage lung cancer as neoadjuvant or adjuvant *** PD-L1 expression and tumor mutational burden have been widely studied for patient selection,both of these biomarkers are *** to the complex cancer-immune interactions among tumor cells,the tumor microenvironment and host immunity,collaborative efforts are needed to establish a multidimensional immunogram to integrate complementary predictive biomarkers for personalized ***,as a result of the wide use of ICIs,managing acquired resistance to ICI treatment remains an inevitable challenge.A deeper understanding of the underlying biological mechanisms of acquired resistance to ICIs is helpful to overcome these *** this review,we describe the cutting-edge progress made in patients with lung cancer,the optimal duration of ICI treatment,ICIs in some special populations,the unique response patterns during ICI treatment,the emerging predictive biomarkers,and our understanding of primary and acquired resistance mechanisms to ICI treatment.

关键词： lung cancer immune-checkpoint inhibitor predictive biomarker acquired resistance

Multi-cancer blood testing combined with PET-CT:road for hope to screen for cancer and guide intervention

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1628-1629页

作者： Tao Jiang Shengxiang Ren caicun zhou Department of Medical Oncology Shanghai Pulmonary Hospital&Thoracic Cancer InstituteTongji University School of MedicineShanghaiChina

In a recent study published in Science,Lennon et al.1 investigated the feasibility and safety of multi-cancer peripheral blood testing in combination with positron emission tomography-computed tomography(PET-CT)imaging to detect cancer in 10,006 women not previously known to have *** findings reveal that multi-cancer blood testing coupled with diagnostic PET-CT can be safely incorporated into routine clinical care to screen for cancer without discouraging patients from engaging in other forms of standard-of-care(SOC)screening;moreover,it is possible to intervene on the basis of blood testing results,in some cases leading to surgery with intent to cure(Fig.1).

关键词： routine cancer al

“新辅助”治疗驱动基因阴性Ⅳ期非小细胞肺癌长期生存1例报告

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中华转移性肿瘤杂志 2024年第2期7卷 161-164页

作者：周斐高广辉周彩存同济大学附属上海市肺科医院肿瘤科上海200433

驱动基因阴性Ⅳ期非小细胞肺癌预后差。本文介绍1例驱动基因阴性Ⅳ期非小细胞肺癌患者,经“新辅助”免疫联合化疗后寡残存病灶行手术切除,病理证实完全缓解,随访4年以上仍维持完全缓解。

关键词：非小细胞肺癌驱动基因阴性免疫治疗

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Non-small cell lung cancer in China

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Cancer Communications 2022年第10期42卷 937-970页

作者： Peixin Chen Yunhuan Liu Yaokai Wen caicun zhou School of Medicine Tongji UniversityShanghai 200092P.R.China Department of Medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghai 200433P.R.China Department of Respiratory and Critical Care Medicine Huadong HospitalFudan UniversityShanghai 200040P.R.China

In China,lung cancer is a primary cancer type with high incidence and mor*** factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung *** early-stage non-small cell lung cancer(NSCLC)patients miss the optimal timing for treatment due to the lack of clinical ***-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in *** understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC,thus prolonging survival in patients with positive *** the exploration of immune escape mechanisms,programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in *** the Chinese Society of Clinical Oncology’s guidelines for NSCLC,maintenance immunotherapy is recommended for locally advanced NSCLC after *** immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable *** this review,we summarized recent advances in NSCLC in China in terms of epidemiology,biology,molecular pathology,pathogenesis,screening,diagnosis,targeted therapy,and immunotherapy。

关键词： non-small cell lung cancer screening targeted therapy immunotherapy epidermal growth factor receptor(EGFR)mutation programmed cell death protein 1(PD-1) programmed deathligand 1(PD-L1) clinical trials clinical guidelines

Recent advances in immunotherapy for lung cancer

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Cancer Innovation 2023年第1期2卷 18-24页

作者： Qi Wang Chunxia Su caicun zhou Department of Oncology Shanghai Pulmonary HospitalTongji UniversityShanghaiChina

Lung cancer is the malignant tumor with the highest morbidity andmortality in China, and nonsmall cell lung cancer is a common form oflung cancer. After undergoing chemotherapy and molecular targetedtherapy, the treatment of lung cancer has now fully entered the era ofimmunotherapy. Immunotherapy‐based treatment has become one of thestandard treatments for lung cancer. Immunotherapy has also graduallymoved from the back line to the front line, from advanced to earlypatients. This article focuses on the latest developments in perioperativeand advanced lung cancer immunotherapy, discusses the problems andchallenges at the current stage, and explores new directions for futuredevelopment.

关键词： nonsmall cell lung cancer small cell lung cancer perioperative period late stage new immunotherapy

EGFR20外显子插入突变非小细胞肺癌规范化诊疗中国专家共识(2024版)

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中国肺癌杂志 2024年第7期27卷 485-494页

作者：中国临床肿瘤学会非小细胞肺癌专家委员会周彩存不详

表皮生长因子受体(epidermal growth factor receptor,EGFR)20外显子插入(exon 20 insertion,ex20ins)突变非小细胞肺癌(non-small cell lung cancer,NSCLC)的规范化诊疗在《EGFR 20外显子插入突变非小细胞肺癌规范化诊疗中国专家共识(2023版)》中进行了阐述,提高了临床医生对该罕见靶点的关注。随着疾病领域探索的深入及新型靶向药物的获批,EGFR ex20ins NSCLC的诊疗策略也随之更新。本共识在2023版中国专家共识的基础上进行更新,专家组通过参考国内外文献及临床数据并结合专家自身临床经验,分别从疾病认知、疾病检测、疾病治疗和新型靶向药物研发现状等方面更新共识性建议,以期更好地为临床医师提供用药参考。

关键词：肺肿瘤 EGFR20外显子插入突变规范化诊疗共识

PD-L1 expression and its effect on clinical outcomes of EGFRmutant NSCLC patients treated with EGFR-TKIs

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Cancer Biology & Medicine 2018年第4期15卷 434-442页

作者： Yuchen Bai Xiaoxia Chen Likun Hou Jun Qian Tao Jiang caicun zhou Maciej Ciebiada Department of General and Oncological Pulmonology University Clinical Hospital Norbert BarlickiMedical University of LodzLodz 50243Poland Department of Urology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Department of Medical Oncology Department of Pathology Shanghai Pulmonary Hospital&Thoracic Cancer InstituteTongji University School of MedicineShanghai 200433China Department of Medical Oncology Suzhou Cancer Centerthe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215000China

Objective:Epidermal growth factor receptor(EGFR)activation was reported to upregulate programmed death-ligand 1(PD-L1)expression in lung cancer cells and subsequently contribute to immune escape,indicating its critical role in EGFR-driven lung *** study characterized PD-L1 expression in patients with surgically resected EGFR-mutant non-small cell lung cancer(NSCLC).The effect of PD-L1 expression on clinical outcomes was also investigated in advanced EGFR-mutant NSCLC treated with EGFR-tyrosine kinase inhibitors(TKIs).Methods:In total,73 patients with surgically resected NSCLC and EGFR mutations were ***-L1 expression and CD8+tumor-infiltrating lymphocyte(TIL)density were assessed by immunohistochemistry.A literature review of publications that assessed the predictive and prognostic value of PD-L1 expression in advanced EGFR-mutant NSCLC patients treated with EGFR-TKIs was ***:Nineteen(26.0%)patients were positive for PD-L1 expression,which was significantly associated with concomitant KRAS mutation(P=0.020)and marginally associated with higher CD8+TILs density(P=0.056).Positive PD-L1 expression was associated with markedly inferior overall survival(OS)in multivariate analysis(P=0.032).The combination of PD-L1 and CD8+TILs expression could be used to stratify the population into three groups with distinct prognoses.A meta-analysis of six publications showed that positive PD-L1 expression was not associated with OS[hazard ratio(HR)=0.90;95%confidence interval(CI),0.42–1.38]or progression-free survival(HR=1.03;95 CI,0.73–1.33)in advanced EGFR-mutant NSCLC patients receiving ***:PD-L1 expression tended to correlate with CD8+TIL expression,concomitant KRAS mutation,and poor survival in surgically resected EGFR-mutant ***-L1 expression was neither the predictive nor the prognostic factor in advanced EGFR-mutant NSCLC patients treated with EGFR-TKIs.

关键词： Non-small cell lung cancer EGFR mutation PD-L1 CD8 survival

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驱动基因阴性非小细胞肺癌二线治疗中国专家共识

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中国肺癌杂志 2024年第2期27卷 81-87页

作者：中国临床肿瘤学会非小细胞肺癌专家委员会周彩存王洁程颖王宝成周清华周斐不详上海市东方医院中国医学科学院肿瘤医院吉林省肿瘤医院解放军第九六〇医院四川大学华西医院上海市肺科医院

对于驱动基因阴性的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者而言,既往化疗一直都是标准治疗选择,而免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的加入为这部分患者提供了新的治疗选择。目前一线治疗可以选... 详细信息

对于驱动基因阴性的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者而言,既往化疗一直都是标准治疗选择,而免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的加入为这部分患者提供了新的治疗选择。目前一线治疗可以选择化疗、抗血管生成药物或免疫治疗。尽管初始治疗能获得一定的有效率,但仍不可避免地会出现疾病进展或治疗失败,二线及以上治疗疗效差,患者预后不佳,临床上需要更多有效的二线治疗药物。中国临床肿瘤学会非小细胞肺癌专家委员会组织呼吸科、肿瘤科、病理科专家对驱动基因阴性人群临床研究证据进行了深入探讨,根据专家组讨论后广泛认可的临床诊疗经验,对驱动基因阴性NSCLC患者二线治疗制定了统一的专家共识,可作为中国临床医师选择驱动基因阴性NSCLC二线治疗的指导依据。

关键词：肺肿瘤免疫治疗抗血管生成药物驱动基因阴性专家共识

维普期刊数据库