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Author Notes:

Corresponding author: Suresh S. Ramalingam, MD, Division of Medical Oncology, Winship Cancer Institute, 1365C Clifton Rd NE, Atlanta, GA 30322; E-mail address: suresh.ramalingam@emory.edu

Suresh S. Ramalingam OrcID: http://orcid.org/0000-0002-0757-3106

Conceptualization: R. Pillai, M. Behera, S. Ramalingam

Methodology: M. Behera, S. Ramalingam

Software: M. Behera

Validation: R. Pillai, M. Behera

Formal analysis: M. Behera

Investigation: R. Pillai, M. Behera, S. Ramalingam

Resources: M. Behera

Data curation: R. Pillai, M. Behera

Writing – original draft: R. Pillai, M. Behera

Writing – review and editing: T. Owonikoko, A. Kamphorst, S. Pakkala, C. Belani, F. Khuri, R. Ahmed, S. Ramalingam

Visualization: R. Pillai

Supervision: S. Ramalingam

Project administration: R. Pillai, M. Behera, S. Ramalingam

Funding acquisition: S. Ramalingam

None of the authors have any conflicts of interest to report.


Research Funding:

This work was supported by P30CA138292 and U10CA180864 grants to Winship Cancer Institute and U10CA180950 grant to ECOG-ACRIN.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • adverse events
  • immune checkpoint inhibitors
  • immune-related adverse events
  • non-small cell lung cancer (NSCLC)
  • RISK

Comparison of the Toxicity Profile of PD-1 Versus PD-L1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Analysis of the Literature


Journal Title:



Volume 124, Number 2


, Pages 271-277

Type of Work:

Article | Post-print: After Peer Review


BACKGROUND: Monoclonal antibodies against programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are effective therapies in patients with non-small cell lung cancer (NSCLC). Herein, the authors performed a systematic review investigating differences in the toxicities of PD-1 and PD-L1 inhibitors. METHODS: An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC. A formal systematic analysis was conducted with Comprehensive Meta-Analysis software (version 2.2). Clinical and demographic characteristics, response, and toxicity data were compared between both groups. RESULTS: A total of 23 studies reported between 2013 and 2016 were eligible for analysis. The total number of patients evaluated for toxicities was 3284 patients in the PD-1 group and 2460 patients in the PD-L1 group. The baseline patient characteristics of the 2 groups were similar, although there was a trend toward increased squamous histology in the group treated with PD-L1 (32% vs 25%; P =.6). There was no difference in response rate noted between PD-1 (19%) and PD-L1 (18.6%) inhibitors (P =.17). The incidence of overall adverse events (AEs) was comparable between the PD-1 and PD-L1 inhibitors (64% [95% confidence interval (95% CI), 63%-66%] vs 66% [95% CI, 65%-69%]; P =.8). Fatigue was the most frequently reported AE with both classes of drugs. Patients treated with PD-1 inhibitors were found to have a slightly increased rate of immune-related AEs (16% [95% CI, 14%-17%] vs 11% [95% CI, 10%-13%]; P =.07) and pneumonitis (4% [95% CI, 3%-5%] vs 2% [95% CI, 1%-3%]; P =.01) compared with patients who received PD-L1 inhibitors. CONCLUSIONS: In this systematic review involving 5744 patients with NSCLC, the toxicity and efficacy profiles of PD-1 and PD-L1 inhibitors appear to be similar. Cancer 2018;124:271-7. © 2017 American Cancer Society.

Copyright information:

© 2017 American Cancer Society

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