Journal ArticleDOI
Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC.
TLDR
In this paper, the authors provide guidance on selecting the optimal ICI-based therapy and highlight several future research directions that will probably further improve the outcomes of patients with advanced-stage non-small-cell lung cancer.Abstract:
The treatment landscape of driver-negative non-small-cell lung cancer (NSCLC) is rapidly evolving. Immune-checkpoint inhibitors, specifically those targeting PD-1 or PD-L1, have demonstrated durable efficacy in a subset of patients with NSCLC, and these agents have become the cornerstone of first-line therapy. Approved immunotherapeutic strategies for treatment-naive patients now include monotherapy, immunotherapy-exclusive regimens or chemotherapy–immunotherapy combinations. Decision making in this space is complex given the absence of head-to-head prospective comparisons, although a thorough analysis of long-term efficacy and safety data from pivotal clinical trials can provide insight into the optimal management of each subset of patients. Indeed, histological subtype and the extent of tumour cell PD-L1 expression are paramount to regimen selection, although other clinicopathological factors and patient preferences might also be relevant in certain scenarios. Finally, several emerging biomarkers and novel therapeutic strategies are currently under investigation, and these might further refine the current treatment paradigm. In this Review, we discuss the current treatment landscape and detail our approach to first-line immunotherapy regimen selection for patients with advanced-stage, driver-negative NSCLC. Immune-checkpoint inhibitors (ICIs) are now standard-of-care therapies for patients with advanced-stage non-small-cell lung cancer (NSCLC) without a targetable driver alteration. Various ICIs or combination regimens have been approved in this setting, relative to chemotherapy, although no prospective data are available comparing the various ICI-based approaches. Here, the authors provide guidance on selecting the optimal ICI-based therapy and highlight several future research directions that will probably further improve the outcomes of patients with advanced-stage NSCLC.read more
Citations
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Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer
TL;DR: In this article , the authors found a significant B cell association with extended OS with PD-L1 blockade, independent of CD8+ T cell signals, and derived gene signatures corresponding to the dominant B cell subsets present in NSCLC from single-cell RNA sequencing (RNA-seq) data.
Journal ArticleDOI
On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial
Tao Jiang,Jianhua Chen,Xingxiang Xu,Ying Chen,Gongyan Chen,Yueyin Pan,Qing Wang,Yunchao Huang,Wen-xiu Yao,Rui Wang,Xing-Ya Li,Wei Zhang,Yanjun Zhang,Shengquan Hu,Renhua Guo,Jian Hua Shi,Zhiwu Wang,Peiguo Cao,Donglin Wang,Jian Fang,Hui Luo,Yingyang Geng,Chunyan Xing,Dongqing Lv,Yiping Zhang,Junyan Yu,Shundong Cang,Yaxi Zhang,Xiao Zhang,Zeyu Yang,Wei Shi,Jianjun Zou,Caicun Zhou,Shengxiang Ren +33 more
TL;DR: Wang et al. as discussed by the authors used on-treatment blood tumor mutation burden (bTMB) and its dynamics to explore their predictive values for lung squamous cell carcinoma (LUSC).
Journal ArticleDOI
On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial
Tao Jiang,Jianhua Chen,Xingxiang Xu,Ying Cheng,Gongyan Chen,Yueyin Pan,Qing Wang,Yunchao Huang,Wen-xiu Yao,Rui Wang,Xing-Ya Li,Wei Zhang,Yanjun Zhang,Sheng-Juan Hu,Renhua Guo,Jian Hua Shi,Zhiwu Wang,Peiguo Cao,Donglin Wang,Jian Fang,Hui Luo,Yijin Geng,Chunyan Xing,Dongqing Lv,Yiping Zhang,Junyan Yu,Shundong Cang,Yaxi Zhang,Xiao Zhang,Zeyu Yang,Wei Shi,Jianjun Zou,Caicun Zhou,Shengxiang Ren +33 more
TL;DR: Wang et al. as discussed by the authors used on-treatment blood tumor mutation burden (bTMB) and its dynamics to explore their predictive values for lung squamous cell carcinoma (LUSC).
Journal ArticleDOI
Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors
Lian Xu,Chang Zou,Shanshan Zhang,Timothy Shun Man Chu,Yan Zhang,Weiwei Chen,Caini Zhao,Lin Yang,Zhiyuan Xu,Shaowei Dong,Hao Yu,Boyan Li,Xinyuan Guan,Yuzhu Hou,Feng Ming Kong +14 more
TL;DR: In this paper , a review of single-cell transcriptomics and spatial transcriptomics for the studies of the systemic tumor immune microenvironment (STIE) and their interactions is presented, which may reveal heterogeneity in immunotherapy responses as well as the dynamic changes essential for the treatment effect.
Journal ArticleDOI
Biomarkers of response to checkpoint inhibitors beyond PD-L1 in lung cancer.
TL;DR: A review of the state of the art in lung cancer immunotherapy response prediction can be found in this article, where the authors address the role of tumor mutation burden as a predictive biomarker, the evolving status of human leukocyte antigen/major histocompatibility complex expression as a marker of antigen presentation, and the importance of tumor genomic profiling to ascertain oncogenic driver (EGFR, ALK, KRAS, MET, etc.) and co-mutation (STK11, KEAP1, SMARCA4) status.
References
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The blockade of immune checkpoints in cancer immunotherapy
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Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer
Hossein Borghaei,Luis Paz-Ares,Leora Horn,D. R. Spigel,M. Steins,Neal Ready,L.Q. Chow,Everett E. Vokes,Enriqueta Felip,Esther Holgado,F. Barlesi,M. Kohlhufl,Oscar Arrieta,Marco Angelo Burgio,J. Fayette,H. Lena,Elena Poddubskaya,David E. Gerber,Scott N. Gettinger,Charles M. Rudin,Naiyer A. Rizvi,L. Crina,G. R. Blumenschein,Scott J. Antonia,C. Dorange,C. T. Harbison,F. Graf Finckenstein,Julie R. Brahmer +27 more
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Journal ArticleDOI
Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer
Martin Reck,Delvys Rodriguez-Abreu,Andrew G. Robinson,Rina Hui,Tibor Csőszi,Andrea Fülöp,Maya Gottfried,Nir Peled,Ali Tafreshi,Sinead Cuffe,Mary O'Brien,Suman Rao,Katsuyuki Hotta,Melanie A. Leiby,Gregory M. Lubiniecki,Yue Shentu,Reshma A. Rangwala,Julie R. Brahmer +17 more
TL;DR: Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express PD-L1 as mentioned in this paper.