Chong Hyun Suh1, Kyung Won Kim1, Junhee Pyo2, Hiroto Hatabu3, 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, 05505, Republic of Korea. 2. WHO Collaborating Center for Pharmaceutical Policy and Regulation, Department of Pharmaceutical Science, Utrecht University, David de Wiedgebouw, Universiteitsweg 99 3584 CG, Utrecht, the Netherlands. 3. Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA, USA. 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
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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