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• The overall incidence of ALK inhibitor pneumonitis was 2.14% in advanced NSCLC. • Patients from Japanese cohorts had a higher incidence of ALK-inhibitor pneumonitis. • Further studies of mechanisms and risk factors of ALK pneumonitis are needed. We evaluated the incidence of pneumonitis in clinical trials of anaplastic lymphoma kinase (ALK) inhibitors in patients with advanced non-small cell lung cancer (NSCLC) and compared the incidence among different cohorts, in order to identify possible predisposing factors for ALK inhibitor-related pneumonitis. MEDLINE and EMBASE search up to 1/30/18 using the keywords, "alectinib", "ceritinib", "crizotinib", "brigatinib", and "lung cancer", resulting in a total of 20 eligible cohorts with 2261 patients treated with ALK inhibitor monotherapy for advanced NSCLC. The pooled incidences of all-grade, high-grade, and grade 5 pneumonitis were calculated. Subgroup analyses were conducted with meta-regression using study-level covariates. The overall pooled incidence of pneumonitis was 2.14% (95% CI: 1.37–3.34) for all grade, 1.33% (95% CI: 0.80–2.21) for high grade, and 0.22% (95% CI: 0.09-0.52) for grade 5 pneumonitis. The incidence was significantly higher in studies from Japan compared to studies of non-Japan origin, for all-grade (6.25% vs 1.14%, p < 0.001) and high-grade pneumonitis (3.31% vs 0.39%, p < 0.001). Multivariate meta-regression demonstrated the cohorts from Japanese studies had significantly higher odds of pneumonitis for all-grade (odds ratio [OR]: 4.329 [95% CI: 1.918, 9.770], p < 0.001) compared to those of non-Japan origin, after adjusting for types of ALK inhibitors. The overall incidence of ALK inhibitor pneumonitis was 2.14% in patients with advanced NSCLS. The patients from Japanese cohorts had a higher incidence of ALK-inhibitor pneumonitis, which indicates the need for increased awareness and caution for pneumonitis in Japanese patients treated with ALK inhibitors. [ABSTRACT FROM AUTHOR]

Purpose: Pneumonitis is a significant toxicity of EGFR tyrosine kinase inhibitors (EGFR-TKI) in non-small-cell lung cancer (NSCLC) patients. We studied the incidence of pneumonitis in clinical trials of EGFR-TKI published in 2003-2017, and performed subgroups analyses to identity predisposing factors., Methods: Ovid-MEDLINE and EMBASE search up to 4/17/17 using the keywords, "erlotinib", "gefitinib", "afatinib", "osimertinib", and "lung cancer", resulted in a total of 153 eligible trial cohorts with 15,713 advanced NSCLC patients treated with EGFR-TKI. The pooled incidence of all-grade, high-grade, and grade 5 pneumonitis was obtained. Subgroup analyses were performed with meta-regression using study-level covariates., Results: Among the patients without prior exposure to EGFR-TKI, the overall incidence was 1.12% (95% CI:0.79-1.58%) for all-grade, 0.61% (95% CI:0.40-0.93%) for high-grade, and 0.20% (95% CI:0.11-0.38%) for grade 5 pneumonitis. The incidence was significantly higher in Japanese studies compared to studies of non-Japan origin, for all-grade (4.77% vs. 0.55%, p < 0.001), high grade (2.49% vs. 0.37%, p < 0.001), and grade 5 pneumonitis (1.00% vs. 0.18%, p < 0.001). Multivariate analyses demonstrated higher odds of pneumonitis in Japanese studies for all-grade (odds ratio [OR]: 5.04; 95% CI:3.14-8.11, p < 0.001), high-grade (OR: 4.45; 95% CI:2.50-7.93, p < 0.001), and grade 5 pneumonitis (OR: 4.55; 95% CI:2.20-9.44, p < 0.001) compared to others, after adjusting for types of EGFR-TKI and lines of therapy. In patients with EGFR retreatment analyzed separately, the pooled incidence was 1.13% (95% CI:0.40-3.15%) for all-grade, 0.49% (95% CI:0.21-1.11%) for high-grade, and 0.16% (95% CI:0.04-0.65%) for grade 5 pneumonitis., Conclusions: The overall incidence of EGFR-TKI pneumonitis was 1.12% in patients without prior exposure to EGFR-TKI, and 1.13% in EGFR-TKI retreatment group. The cohorts from Japan had significantly higher incidence of pneumonitis, providing insights for further mechanistic studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)