Immune Checkpoint Inhibition With Chemoradiotherapy in Stage III Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis of Safety Results

Balasubramanian, A; Onggo, J; Gunjur, A; John, T; Parakh, S

Author(s): Balasubramanian, A; Onggo, J; Gunjur, A; John, T; Parakh, S;
Details: Publication Year 2021-03,Volume 22,Issue #2,Page 74-82
Journal Title: Clinical Lung Cancer
Publication Type: Review
Abstract: The role of immune checkpoint inhibitors (ICIs) administered concurrently with or after definitive chemoradiation (CRT) in stage III non-small-cell lung cancer (NSCLC) has been detailed in several studies. We performed a systematic review to determine pneumonitis rates using ICIs with CRT. MEDLINE and EMBASE databases were searched using keywords and MeSH terms. Studies using anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) therapy, either sequentially or concurrently with CRT, for patients with stage III NSCLC were included. A meta-analysis of pneumonitis rates was performed based on weighted pooled proportion, using random-effects models. Weighting was performed by the inverse variance or standard error of event rates. Comparative analysis between groups was performed. Odds ratios (OR) were used as the primary summary statistics. A total of 13 studies were identified (6 prospective clinical trials and 7 real-world reports). Rates of grade >/= 3 pneumonitis were significantly higher in clinical trials using anti-PD-1 therapy compared with PD-L1 inhibitors (8.6%; 95% confidence interval [CI], 6.2%-11.9% vs. 4.4%; 95% CI, 3.0%-6.6%; OR, 2.0; P = .01). Clinical trials using concurrent ICI therapy with CRT had greater rates of grade 2 pneumonitis compared with sequential administration (23.0%; 95% CI, 15.8%-32.3% vs. 11.0%; 95% CI, 6.6%-17.8%; OR, 0.42; P = .02). Higher rates of grade >/= 3 pneumonitis were observed in real-world studies compared with clinical trials involving sequential PD-L1 therapy (9.9%; 95% CI, 5.3%-17.9% vs. 4.4%; 95% CI, 2.9%-6.7%; OR, 0.43; P < .01). The suggestion of increased pneumonitis with a concurrent ICI strategy and using anti-PD-1 therapies warrants further consideration in future comparative studies.
Keywords: Aged; B7-H1 Antigen/antagonists & inhibitors; Carcinoma, Non-Small-Cell Lung/pathology/*therapy; Chemoradiotherapy; Humans; Immune Checkpoint Inhibitors/adverse effects/*therapeutic use; Immunotherapy; Lung Neoplasms/pathology/*therapy; Middle Aged; Neoplasm Staging; Pneumonia/chemically induced; Programmed Cell Death 1 Receptor/antagonists & inhibitors; Treatment Outcome; Durvalumab; Nsclc; PD-1 inhibitors; PD-L1 inhibitors
Department(s): Medical Oncology
PubMed ID: 33414053
Publisher's Version: https://doi.org/10.1016/j.cllc.2020.10.023
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-05-30 08:01:30

Last Modified: 2025-05-30 08:02:20