Zhuo Ma1, Ximu Sun2, Zhixia Zhao1, Wenchao Lu1, Qixiang Guo1, Shihao Wang3, Jiwen You3, Yuhui Zhang4, Lihong Liu5. 1. Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, China. 2. Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No.17, Qi He Lou Street, Dongcheng District, Beijing, China. 3. AI Research Division, A.I. Phoenix Technology Co., Ltd, RM1080, LV 10, CENTRAL BLD, 1-3 PEDDER ST, CENTRAL, Hong Kong, China. 4. Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Institute of Respiratory Medicine, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, China. Electronic address: zhangyhcy@ccmu.edu.com. 5. Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, China. Electronic address: liulihong@bjcyh.com.
Abstract
OBJECTIVE/ BACKGROUND: We aimed to evaluate the risk of PARP inhibitors (PARPis) causing pneumonitis in randomized controlled trials (RCTs) and in the real-world practice. METHODS: First, a systematic review based on meta-analysis was conducted. RCTs with available data reporting pneumonitis events for PARPis were eligible for analysis. Second, we conducted a disproportionality analysis based on data from the FDA Adverse Event Reporting System (FAERS) database to characterize the main features of PARPi-related pneumonitis. RESULTS: 16 trials with 5771 patients were included in our meta-analysis. Compared with control arms, PARPis showed a significant increase in the risk of pneumonitis events (Peto OR 2.68 [95% CI 1.31-5.47], p = 0.007) with no heterogeneity (I2 = 0%, χ2p = 0.70). The incidence of pneumonitis across treatment arms was 0.79% (28/3551). In the FAERS database, we identified 84 cases of PARPi-pneumonitis with a fatality rate of 16% (13/79). The median time to event onset was 81 (interquartile range [IQR] 27-131) days and 87% of the adverse events occurred within 6 months. CONCLUSION: PARPis increased the risk of pneumonitis that can result in serious outcomes and tend to occur early. Early recognition and management of PARPi-pneumonitis is of vital importance in clinical practice. The mechanisms and risk factors should be studied further to improve clinical understanding and innovative treatment strategies for these diseases.
OBJECTIVE/ BACKGROUND: We aimed to evaluate the risk of PARP inhibitors (PARPis) causing pneumonitis in randomized controlled trials (RCTs) and in the real-world practice. METHODS: First, a systematic review based on meta-analysis was conducted. RCTs with available data reporting pneumonitis events for PARPis were eligible for analysis. Second, we conducted a disproportionality analysis based on data from the FDA Adverse Event Reporting System (FAERS) database to characterize the main features of PARPi-related pneumonitis. RESULTS: 16 trials with 5771 patients were included in our meta-analysis. Compared with control arms, PARPis showed a significant increase in the risk of pneumonitis events (Peto OR 2.68 [95% CI 1.31-5.47], p = 0.007) with no heterogeneity (I2 = 0%, χ2p = 0.70). The incidence of pneumonitis across treatment arms was 0.79% (28/3551). In the FAERS database, we identified 84 cases of PARPi-pneumonitis with a fatality rate of 16% (13/79). The median time to event onset was 81 (interquartile range [IQR] 27-131) days and 87% of the adverse events occurred within 6 months. CONCLUSION: PARPis increased the risk of pneumonitis that can result in serious outcomes and tend to occur early. Early recognition and management of PARPi-pneumonitis is of vital importance in clinical practice. The mechanisms and risk factors should be studied further to improve clinical understanding and innovative treatment strategies for these diseases.
Authors: Jamila Mammadova; Anna Redden; Rachel Cruz; Maryssa Ellison; Tyra Gatewood; Carla Duff; Anthony Canella; Charurut Somboonwit; Chakrapol Sriaroon; Joseph F Dasso; Terry Harville; Roohi Ismail-Khan; Jolan E Walter; Sumai Gordon Journal: Front Oncol Date: 2022-06-29 Impact factor: 5.738