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

• Type of Material: Article
• Authors: Rathi Pillai, Emory University; Madhusmita Behera, Emory University; Taofeek Owonikoko, Emory University; Alice O. Kamphorst, Emory University; Suchita Pakkala, Emory University; Chandra P. Belani, Pennsylvania State University; Fadlo Khuri, Emory University; Rafi Ahmed, Emory University; Suresh Ramalingam, Emory University
• Language: English
• Date: 2018-01-15
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 American Cancer Society
• Final Published Version (URL): http://dx.doi.org/10.1002/cncr.31043
• Title of Journal or Parent Work: Cancer
• ISSN: 0008-543X
• Volume: 124
• Issue: 2
• Start Page: 271
• End Page: 277
• Grant/Funding Information: This work was supported by P30CA138292 and U10CA180864 grants to Winship Cancer Institute and U10CA180950 grant to ECOG-ACRIN.
• Keywords: COMPUTED-TOMOGRAPHY; non-small cell lung cancer (NSCLC); immune checkpoint inhibitors; REDUCTION; immune-related adverse events; DIAGNOSIS; Oncology; adverse events; NODULES; TRIAL; Life Sciences & Biomedicine; BIOMARKER; Science & Technology; RISK
• Research Categories: Health Sciences, Oncology; Health Sciences, Immunology

Abstract

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.