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Original research
Impact of PD1 and PDL1 immunotherapy on non-small cell lung cancer outcomes: a systematic review
  1. Shivani Setur Kanabar1,2,
  2. Abhinav Tiwari1,
  3. Vina Soran1,
  4. Prashanthan Balendran1,
  5. Malcolm Price2,3,
  6. Alice Margaret Turner2
  1. 1Medical School, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK
  2. 2Institute of Applied Health Research, University of Birmingham, Birmingham, UK
  3. 3NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  1. Correspondence to Ms Shivani Setur Kanabar, Medical School, University of Birmingham College of Medical and Dental Sciences, Birmingham, Birmingham, UK; shivani.kanabar{at}outlook.com

Abstract

Introduction Despite comprising many cancer diagnoses, few treatments are suitable for patients with advanced non-small cell lung cancer (aNSCLC). Trials suggest blockade of programmed death 1 (PD1) or its ligand (PDL1) may be effective for these patients. However, this therapy’s impact on outcomes other than survival, and outcomes of patients not in trials, remains largely unknown. Therefore, we compared the effectiveness of PD1 and PDL1 immunotherapy to chemotherapy and placebo across multiple clinical outcomes.

Methods Six databases were searched on 12–13 October 2019 for randomised controlled trials (RCTs) and observational studies investigating nivolumab, pembrolizumab, atezolizumab or durvalumab. Study selection was performed independently by two reviewers. Data for overall survival, progression-free survival, adverse effects (AEs) and quality of life (QoL) were descriptively and meta-analysed. Factors impacting treatment outcomes, including PDL1 expression, were explored. The similarity between RCT and observational data was assessed.

Results From 5423 search results, 139 full texts and abstracts were included. Immunotherapy was associated with a lower risk of death than both comparators. In RCTs, the incidence of treatment-related AEs was approximately 20% lower among patients using immunotherapy compared with chemotherapy. However, no other consistent benefits were observed. Progression-free survival results were inconsistent. Improvements to QoL varied according to the instrument used; however, QoL was not recorded widely. Survival results were similar between study designs; however, AEs incidence was lower in observational studies.

Discussion Among patients with aNSCLC, immunotherapy improved overall survival and incidence of treatment-related AEs compared with chemotherapy. Benefits to progression-free survival and QoL were less consistent.

PROSPERO registration number CRD42019153345.

  • lung cancer
  • non-small cell lung cancer

Data availability statement

Data are available upon reasonable request. Given the large number of studies included in this review, not all data gathered could be included in the article. However, we have kept a database of all data collected pertaining to this review, which can be made available upon request.

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Data availability statement

Data are available upon reasonable request. Given the large number of studies included in this review, not all data gathered could be included in the article. However, we have kept a database of all data collected pertaining to this review, which can be made available upon request.

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Footnotes

  • Twitter @ShivaniKanabar

  • Contributors SSK was the lead author of the study and is the content guarantor. The roles included were planning study methods; writing the PROSPERO protocol; literature searches; screening study titles and abstracts; checking inclusions and exclusions, and bias assessments of relevant studies; data analysis and writing and editing the submitted manuscript. The roles of AT were screening study titles and abstracts, screening relevant studies, extracting data from included studies and completing the primary risk of bias assessments. The roles of VS and PB were screening relevant studies, extracting data from included studies and completing the primary risk of bias assessments. The roles of MP were assisting in the editing of figures, assisting in the meta-analysis of data, and editing the submitted manuscript. AMT was the supervisor of the study. The roles included were planning study methods, editing the PROSPERO protocol, screening study titles and abstracts, and writing and editing the submitted manuscript. All authors commented on drafts of the article and have approved the final version.

  • Competing interests None declared.

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

  • 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.

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