Pneumonitis, or drug-induced interstitial lung disease (ILD), is a rare, potentially serious immune-mediated AE associated with PD-1 inhibitors such as pembrolizumab (pembro; MK-3475). We characterized the clinical course of and potential risk factors for pneumonitis in the 550 patients (pts) with advanced NSCLC enrolled in KEYNOTE-001 (ClinicalTrials.gov, NCT01295827).
Pts with previously treated or treatment-naive advanced NSCLC received pembro 10 mg/kg Q2W (n = 202), 10 mg/kg Q3W (n = 287), or 2 mg/kg Q3W (n = 61). Pneumonitis was quantitatively assessed using the following MedDRA terms, regardless of grade or investigator assessment of causality: acute interstitial pneumonitis, ILD, pneumonitis, and idiopathic pneumonia syndrome. Baseline demographics and treatment history were analyzed to identify potential risk factors.
As of the January 2015 cutoff date, median time on treatment was 99 d (range, 1-925), and the median number of pembro doses was 6 (range, 1-45). Incidence of any-grade and grade 3-5 pneumonitis was 3.8% (n = 21) and 2.0% (n = 11). Incidence was generally similar across schedules and by percentage of tumor cells with PD-L1 staining but was higher in pts with a history of asthma or COPD (5.3%) or those with a history of thoracic radiation (6.0%). Histology, age, race, smoking history, and previous chemotherapy had no impact on incidence. One pt died and 12 (2.2%) pts discontinued pembro due to pneumonitis. Median time to onset was 57 d (range, 4-393), and median duration per episode was 40 d (range, 5-523+ d). High-dose corticosteroids were used to manage pneumonitis in 16 of 21 pts (76.2%); median starting dose was 78 mg/d (range, 50-156), and median duration at that dose was 8 d (range, 1-128). Pneumonitis initially resolved in 11 pts (52.4%). Of the 4 pts retreated with pembro, pneumonitis recurred in 1 (25.0%).
In this large cohort of pembro-treated advanced NSCLC pts, pneumonitis incidence is generally low. Pneumonitis was generally effectively managed by holding pembro and use of corticosteroids. Results of ongoing randomized trials will elucidate the relative risk of pneumonitis with pembro compared with standard chemotherapy in pts with advanced NSCLC.
Clinical trial identification
M.-J. Ahn: Advisory board member for AstraZeneca, Eli Lilly, and Boehringer Ingelheim. L. Gandhi: received honoraria from Merck & Co., Inc. Consultant/advisor for Merck & Co., Inc. and Genentech/Roche; received travel reimbursement from Merck & Co., Inc. and Genentech/Roche. O. Hamid: Advisory board member for and received research grants from Merck & Co., Inc. M.D. Hellmann: Advisory board member for Genentech and BMS; received research grants from Merck & Co., Inc., BMS, Genentech, Incyte, and Eli Lilly; consultant for Third Rock Ventures and Inovio Pharmaceuticals. E.B. Garon: received research grants from AstraZeneca, BMS, Eli Lilly, Heat, Genentech, Merck & Co., Inc., Novartis, and Pfizer. S.S. Ramalingam: Advisory board member for AstraZeneca, Merck & Co., Inc., Genentech, and BMS. G.M. Lubiniecki, J. Zhang: employee of Merck & Co., Inc. B. Piperdi: employee of and owns stock in Merck & Co., Inc. R. Hui: Advisory board member for Merck Sharp & Dohme, Pfizer, and AstraZeneca.