Chong Hyun Suh1, Hye Sun Park2, Kyung Won Kim1, Junhee Pyo3, Hiroto Hatabu2, Mizuki Nishino4. 1. Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea. 2. Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston MA, USA. 3. WHO Collaborating Center for Pharmaceutical Policy and Regulation, Department of Pharmaceutical Science, Utrecht University, David de Wiedgebouw, Universiteitsweg 99 3584 CG Utrecht, Netherlands. 4. Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston MA, USA. Electronic address: Mizuki_Nishino@DFCI.HARVARD.EDU.
Abstract
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.
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 NSCLCpatients 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.
Authors: Maik Häntschel; Johannes Niebling; Almut Häring; Max-Felix Häring; Thorben Groß; Marius Horger; Reimer Riessen; Michael Haap; Richard A Lewis; Michael Böckeler; Jürgen Hetzel Journal: Thorac Cancer Date: 2020-05-06 Impact factor: 3.500
Authors: Oscar Arrieta; Andrés F Cardona; Luis Lara-Mejía; David Heredia; Feliciano Barrón; Zyanya Lucia Zatarain-Barrón; Francisco Lozano; Vladmir Cordeiro de Lima; Federico Maldonado; Francisco Corona-Cruz; Maritza Ramos; Luis Cabrera; Claudio Martin; Luis Corrales; Mauricio Cuello; Marisol Arroyo-Hernández; Enrique Aman; Ludwing Bacon; Renata Baez; Sergio Benitez; Antonio Botero; Mauricio Burotto; Christian Caglevic; Gustavo Ferraris; Helano Freitas; Diego Lucas Kaen; Sebastián Lamot; Gustavo Lyons; Luis Mas; Andrea Mata; Clarissa Mathias; Alvaro Muñoz; Ana Karina Patane; George Oblitas; Luis Pino; Luis E Raez; Jordi Remon; Leonardo Rojas; Christian Rolfo; Alejandro Ruiz-Patiño; Suraj Samtani; Lucia Viola; Santiago Viteri; Rafael Rosell Journal: Crit Rev Oncol Hematol Date: 2020-06-20 Impact factor: 6.312