Everolimus-Induced Pneumonitis in Patients with Neuroendocrine Neoplasms: Multinational Study on Risk Factors and Outcomes

Introduction: The incidence and risk factors for everolimus-induced pneumonitis (EiP) have been poorly studied in patients (pts) with neuroendocrine neoplasms (NEN) outside of clinical trials. Aim(s): To evaluate the incidence, risk factors, treatment patterns and outcomes among eligible pts. Materials and methods: A retrospective multinational cohort of consecutive pts with advanced NEN who received at least one dose of everolimus (eve). Imaging reports were reviewed for pneumonitis (correlation between radiologic and clinical judgment). Clinical features, data on eve and treatment profiles for EiP were summarized. Overall survival was calculated with the Kaplan-Meier method. Results: A total of 122 pts from two centers were included: median age at start of eve was 62 (19-86) years and 62% were males. Nearly half were from pancreatic origin (62, 51%) vs. non-pancreatic NEN. Twenty-eight pts (23%; 95% CI 16-31%) developed EiP: 82% were G1 or 2, 14% G3 and 4% G1. The median duration on eve was 6.9 (0.2-117) months and the median time to EiP was 3.6 (0.8-50) months. Primary site, concurrent lung disease, smoking history, prior therapies were not associated with EiP. Dose reduction due to EiP was needed in 16%, while temporarily and permanent discontinuation occurred 12% and 6%, respectively. EiP resolved in 64% of cases and 25% recovered with minor sequelae. Pts with EiP had a trend for better survival (median 76 vs. 52 months, P=0.093). Conclusion: EiP is present in nearly one quarter of NEN, often occurs in the first months of eve and are mostly uncomplicated. While we could not identify risk factors for EiP, we observed a trend for improved survival among pts with EiP.