Article Text

Original research
Indirect comparison between immunotherapy alone and immunotherapy plus chemotherapy as first-line treatment for advanced non-small cell lung cancer: a systematic review
  1. Lingling Li1,
  2. Fei Xu2,
  3. Yu Chen1,
  4. Xiaoli Ren3,
  5. Yu Liu1,
  6. Yuan Chen1,
  7. Shu Xia1
  1. 1Department of Oncology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
  2. 2Department of Oncology, Affiliated Hospital of Hebei University of Engineering, Handan, China
  3. 3Department of Hematology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, China
  1. Correspondence to Dr Shu Xia; xiashutj{at}


Objectives Use of immune checkpoint inhibitors as first-line treatment for advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) remains controversial. Clinical trials comparing single-drug immunotherapy (IO) with immunotherapy plus chemotherapy (IC) are lacking. We aimed to compare the efficacy of IO alone with that of IC as first-line treatment for advanced NSCLC.

Design Systematic review.

Data sources PubMed, the Cochrane Library and Embase for related studies on NSCLC;, American Society of Clinical Oncology Meeting Library and World Conference on Lung Cancer for relevant conference abstracts (to July 2019).

Eligibility criteria Articles meeting the following criteria were selected: (1) randomised controlled trials on NSCLC treatment, (2) all individuals in the studies had not received treatment previously and (3) research on IO monotherapy using programmed death-1/programmed death ligand-1 (PD-L1) inhibitors or IC.

Data extraction and synthesis After reading the original literature, two reviewers independently extracted the relevant information. The primary outcomes were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). We also extracted data on treatment-related adverse events and immune-related adverse events (irAEs).

Results Overall, 10 randomised controlled clinical trials (n=5765) were included. As first-line treatment for advanced NSCLC, IC tended to yield better PFS, OS and ORR than did IO. Furthermore, IC yielded significantly better PFS than IO when tumour PD-L1 expression was at least 50% (HR: 1.81, 95% CI: 1.18 to 2.78) and yielded a better OS and PFS when tumour PD-L1 expression was at least 1%; IO resulted in fewer adverse events than did IC. However, the incidence of irAEs was higher for IO than for IC.

Conclusions The findings of the indirect comparison indicate that IC as first-line treatment for advanced NSCLC is significantly more effective than IO in patients with PD-L1 expression in at least 50% of tumour cells.

Trial registration number CRD 42018116589.

  • oncology
  • adult oncology
  • immunology

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

View Full Text

Statistics from

Supplementary materials


  • Contributors LL, FX and YC contributed to the collection and evaluation of data and statistical analysis. LL wrote the manuscript. XR and YL contributed to the interpretation of data. SX and YC contributed to the study design, statistical analysis and interpretation of results. All authors contributed to the revision of the manuscript.

  • Funding This work was supported by the Double First-Class University Plan funding of 2016 from Tongji Medical College, Huazhong University of Science and Technology (grant no. 5001540022) and the Hubei Provincial Health Planning Commission (grant no. WJ2017M082).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. Extra data can be accessed via the Dryad data repository at with the doi:10.5061/dryad.0gb5mkkzv.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.