Pembrolizumab as the first-line monotherapy for non-small-cell lung cancer with a low programmed death ligand 1 threshold

  • Zhijie Xu
  • Xiang Wang
  • Xi Chen
  • Shuangshuang Zeng
  • Zhicheng Gong
  • Yuanliang YanEmail author
Bits and Bytes


Pembrolizumab monotherapy has been demonstrated as a first-line therapy for non-small-cell lung cancer (NSCLC) patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%; however, the clinical efficacy is limited by the unreasonable threshold of the TPS. A recent study published by Mok et al. (Lancet 393:1819–1830, 2019) showed that pembrolizumab monotherapy could also be extended as an effective first-line therapeutic strategy for NSCLC patients with low TPS. However, this needs to be further evaluated in detail after considering the following issues. In Mok’s report, the survival curves were much lower in a pembrolizumab-treated group in the first 6 months of treatment compared with a chemotherapy group. These contradictory findings might have been due to anecdotal occurrences of rapid progression, especially hyperprogressive disease.


Pembrolizumab NSCLC PD-L1 TPS Hyperprogressive disease 



This work was supported by National Natural Science Foundation of China (81703036 and 81803035).

Authors’ contributions

Conception and design: Z.J. Xu, X. Wang, X. Chen, S.S. Zeng, and Z.C. Gong. Writing, review, and/or revision of the manuscript: Z.J. Xu and Y.L. Yan. Administrative, technical, and/or material support: X. Wang and S.S. Zeng.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.


  1. Antonia SJ et al (2019) Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis. Lancet Oncol 20:1395–1408. CrossRefPubMedGoogle Scholar
  2. Arbour KC, Riely GJ (2019) Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review. JAMA 322:764–774. CrossRefPubMedGoogle Scholar
  3. Champiat S, Ferrara R, Massard C, Besse B, Marabelle A, Soria JC, Ferte C (2018) Hyperprogressive disease: recognizing a novel pattern to improve patient management. Nat Rev Clin Oncol 15:748–762. CrossRefPubMedGoogle Scholar
  4. Ferrara R et al (2018) Hyperprogressive disease in patients with advanced non-small cell lung Cancer treated with PD-1/PD-L1 inhibitors or with single-agent chemotherapy. JAMA Oncol 4:1543–1552. CrossRefPubMedPubMedCentralGoogle Scholar
  5. Herbst RS, Morgensztern D, Boshoff C (2018) The biology and management of non-small cell lung cancer. Nature 553:446–454. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Kordbacheh T, Honeychurch J, Blackhall F, Faivre-Finn C, Illidge T (2018) Radiotherapy and anti-PD-1/PD-L1 combinations in lung cancer: building better translational research platforms. Annals of oncology : official journal of the European Society for Medical Oncology 29:301–310. CrossRefGoogle Scholar
  7. Mok TSK et al (2019) Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 393:1819–1830. CrossRefPubMedGoogle Scholar
  8. Peters S, Reck M, Smit EF, Mok T, Hellmann MD (2019) How to make the best use of immunotherapy as first-line treatment for advanced/metastatic non-small-cell lung cancer. Annals of oncology : official journal of the European Society for Medical Oncology.
  9. Zuazo M, Gato-Canas M, Llorente N, Ibanez-Vea M, Arasanz H, Kochan G, Escors D (2017) Molecular mechanisms of programmed cell death-1 dependent T cell suppression: relevance for immunotherapy. Annals of translational medicine 5:385. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The International CCN Society 2020

Authors and Affiliations

  1. 1.Department of PathologyXiangya Hospital, Central South UniversityChangshaChina
  2. 2.National Clinical Research Center for Geriatric DisordersXiangya Hospital, Central South UniversityChangshaChina
  3. 3.Department of PharmacyXiangya Hospital, Central South UniversityChangshaChina

Personalised recommendations