Defining adverse events of anti-programmed-death-1 (Anti-PD1) agents using FDA adverse event reporting system (FAERS).

Abstract

e14568 Background: Anti-PD1 inhibitors are a promising therapeutic option in oncology. They have received FDA-approval in treating metastatic and relapsed non-small cell lung cancer, kidney cancer, head-and-neck cancer, and melanoma. Yet its adverse event profile is still being defined. The FAERS database contains information on adverse events and medication error reports submitted to the FDA and serves to support the post-marketing safety surveillance program for drug and therapeutic biologic products. Methods: We searched the FAERS database from January 1, 2015 to June 30, 2016. Only initial cases reported by an MD or pharmacist for treatment of cancers of the lung, kidney, head and neck, or melanoma were included. Cases with incomplete starting, ending or event dates were excluded. The primary outcome was time from drug initiation to onset of the event. Cox proportional hazard model was used to evaluate the association between time to AE and age, gender, disease, and time of report. Results: A total of 105 adverse events (AEs) were identified. Of those AEs, 68 were related to nivolumab, 35 to pembrolizumab, and 2 to atezolizumab. Fifty-six AEs were seen in lung cancer patients, whereas 46 were in melanoma, 2 in kidney cancer and 1 in a head and neck cancer patient. Thirty-three AEs involved pulmonary complications, 30 gastrointestinal systems, 17 endocrine, and 9 were constitutional in nature. The median onset of AEs from the start of therapy was 31 days (range: 2 - 459 days). Using a Cox regression analysis, pembrolizumab was associated with a longer time to AEs compared to nivolumab (HR 0.48, 95%CI: 0.26 - 0.89). Also age between 60 and 70 was associated with a longer time to the onset of AEs compared to age < 60 (HR 0.61, 95%CI: 0.37-0.99). Conclusions: FAERS is a vigilance system to monitor AEs from anti-PD1 inhibitors. Pembrolizumab and age between 60 and 70 were associated with less AEs. Ongoing data accrual will increase the statistical power and analysis of AEs from anti-PD1 inhibitors in greater detail.