Emerging Evidence and Treatment Paradigm of Non-small Cell Lung Cancer

Overview

Journal J Hematol Oncol

Publisher Biomed Central

Specialties Hematology
Oncology

Date 2023 Apr 18

PMID 37069698

Authors

Si-Yang Maggie Liu

Mei-Mei Zheng

Yi Pan

Si-Yang Liu

Yangqiu Li

Yi-Long Wu

Affiliations

Soon will be listed here.

Abstract

Research on biomarker-driven therapy and immune check-point blockade in non-small cell lung cancer (NSCLC) is rapidly evolving. The width and depth of clinical trials have also dramatically improved in an unprecedented speed. The personalized treatment paradigm evolved every year. In this review, we summarize the promising agents that have shifted the treatment paradigm for NSCLC patients across all stages, including targeted therapy and immunotherapy using checkpoint inhibitors. Based on recent evidence, we propose treatment algorithms for NSCLC and propose several unsolved clinical issues, which are being explored in ongoing clinical trials. The results of these trials are likely to impact future clinical practice.

Citing Articles

A comprehensive prognostic and immunological implications of Gremlin 1 in lung adenocarcinoma.

Li H, Zhou Y, Xiao J, Liu F Front Immunol. 2025; 16:1529195.

PMID: 40066442 PMC: 11891240. DOI: 10.3389/fimmu.2025.1529195.

Methodology of murine lung cancer mimics clinical lung adenocarcinoma progression and metastasis.

Kim E, Kim E, Knott E, Wang Y, Chen C, Conejo-Garcia J Sci Rep. 2025; 15(1):7127.

PMID: 40021683 PMC: 11871348. DOI: 10.1038/s41598-025-90344-1.

Hsa_circ_0000515 sequesters microRNA-296-5p and elevates RNF44 expression to encourage the NSCLC progression.

Sun L, Lu B, Li C, Xu G J Cell Commun Signal. 2025; 19(1):e70005.

PMID: 39995883 PMC: 11850089. DOI: 10.1002/ccs3.70005.

MVASA-HGN: multi-view adaptive semantic-aware heterogeneous graph network for mutation status prediction.

Yang W, Yoshida S, Zhao J, Wu W, Qiang Y Quant Imaging Med Surg. 2025; 15(2):1190-1211.

PMID: 39995744 PMC: 11847186. DOI: 10.21037/qims-24-1370.

Integrated analysis of M2 macrophage-related gene prognostic model and single-cell sequence to predict immunotherapy response in lung adenocarcinoma.

Li M, Wang Z, Huang B, Lai Y, Zhang M, Lin C Front Genet. 2025; 16:1519677.

PMID: 39963673 PMC: 11830816. DOI: 10.3389/fgene.2025.1519677.

References

Kirsten W, Mayer L . Morphologic responses to a murine erythroblastosis virus. J Natl Cancer Inst. 1967; 39(2):311-35. View

Drilon A, Tan D, Lassen U, Leyvraz S, Liu Y, Patel J . Efficacy and Safety of Larotrectinib in Patients With Tropomyosin Receptor Kinase Fusion-Positive Lung Cancers. JCO Precis Oncol. 2022; 6:e2100418. PMC: 8830513. DOI: 10.1200/PO.21.00418. View

Scagliotti G, Pastorino U, Vansteenkiste J, Spaggiari L, Facciolo F, Orlowski T . Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non-small-cell lung cancer. J Clin Oncol. 2011; 30(2):172-8. DOI: 10.1200/JCO.2010.33.7089. View

Mok T, Wu Y, Thongprasert S, Yang C, Chu D, Saijo N . Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009; 361(10):947-57. DOI: 10.1056/NEJMoa0810699. View

Pillai R, Behera M, Berry L, Rossi M, Kris M, Johnson B . HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium. Cancer. 2017; 123(21):4099-4105. PMC: 5650517. DOI: 10.1002/cncr.30869. View

Arcila M, Chaft J, Nafa K, Roy-Chowdhuri S, Lau C, Zaidinski M . Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res. 2012; 18(18):4910-8. PMC: 3865806. DOI: 10.1158/1078-0432.CCR-12-0912. View

Antonia S, Villegas A, Daniel D, Vicente D, Murakami S, Hui R . Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 377(20):1919-1929. DOI: 10.1056/NEJMoa1709937. View

Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot A, Mezquita L . Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019; 30(8):1321-1328. PMC: 7389252. DOI: 10.1093/annonc/mdz167. View

Chansky K, Detterbeck F, Nicholson A, Rusch V, Vallieres E, Groome P . The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol. 2017; 12(7):1109-1121. DOI: 10.1016/j.jtho.2017.04.011. View

10.

Katipally R, Pitroda S, Juloori A, Chmura S, Weichselbaum R . The oligometastatic spectrum in the era of improved detection and modern systemic therapy. Nat Rev Clin Oncol. 2022; 19(9):585-599. DOI: 10.1038/s41571-022-00655-9. View

11.

Liu S, Wu Y . An immunological storm for cancer therapy: 2018 Nobel Prize in Physiology or Medicine. Sci Bull (Beijing). 2023; 63(24):1608-1610. DOI: 10.1016/j.scib.2018.11.023. View

12.

Chaudhuri A, Chabon J, Lovejoy A, Newman A, Stehr H, Azad T . Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling. Cancer Discov. 2017; 7(12):1394-1403. PMC: 5895851. DOI: 10.1158/2159-8290.CD-17-0716. View

13.

Skoulidis F, Goldberg M, Greenawalt D, Hellmann M, Awad M, Gainor J . Mutations and PD-1 Inhibitor Resistance in -Mutant Lung Adenocarcinoma. Cancer Discov. 2018; 8(7):822-835. PMC: 6030433. DOI: 10.1158/2159-8290.CD-18-0099. View

14.

Gainor J, Shaw A, Sequist L, Fu X, Azzoli C, Piotrowska Z . EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non-Small Cell Lung Cancer: A Retrospective Analysis. Clin Cancer Res. 2016; 22(18):4585-93. PMC: 5026567. DOI: 10.1158/1078-0432.CCR-15-3101. View

15.

Sun L, Hsu M, Cohen R, Langer C, Mamtani R, Aggarwal C . Association Between KRAS Variant Status and Outcomes With First-line Immune Checkpoint Inhibitor-Based Therapy in Patients With Advanced Non-Small-Cell Lung Cancer. JAMA Oncol. 2021; 7(6):937-939. PMC: 8050787. DOI: 10.1001/jamaoncol.2021.0546. View

16.

Nogami N, Barlesi F, Socinski M, Reck M, Thomas C, Cappuzzo F . IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain. J Thorac Oncol. 2021; 17(2):309-323. DOI: 10.1016/j.jtho.2021.09.014. View

17.

Passaro A, Brahmer J, Antonia S, Mok T, Peters S . Managing Resistance to Immune Checkpoint Inhibitors in Lung Cancer: Treatment and Novel Strategies. J Clin Oncol. 2022; 40(6):598-610. DOI: 10.1200/JCO.21.01845. View

18.

Evison M . The current treatment landscape in the UK for stage III NSCLC. Br J Cancer. 2020; 123(Suppl 1):3-9. PMC: 7735211. DOI: 10.1038/s41416-020-01069-z. View

19.

Tsurutani J, Iwata H, Krop I, Janne P, Doi T, Takahashi S . Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors. Cancer Discov. 2020; 10(5):688-701. PMC: 8292921. DOI: 10.1158/2159-8290.CD-19-1014. View

20.

Grant M, Herbst R, Goldberg S . Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC. Nat Rev Clin Oncol. 2021; 18(10):625-644. DOI: 10.1038/s41571-021-00520-1. View