Drug-related pneumonitis during everolimus therapy in patients with metastatic breast cancer: Incidence, radiographic findings, and correlation with clinical outcome.

Abstract

e12519 Background: Everolimus (EVE) in combination with endocrine therapy are approved for the treatment of HR+/HER2- metastatic breast cancers (MBC) patients. mTOR inhibitor-associated pneumonitis is one of the most worrying and common adverse drug events leading to treatment discontinuation. We investigated the incidence of drug-related pneumonitis (DRP) during EVE therapy in MBC patients and characterize radiographic patterns and clinical impact of pneumonitis. Methods: We retrospectively reviewed the data of MBC patients treated with EVE in Fudan University Shanghai Cancer Center from June 2013 to June 2017, who had baseline and at least one follow-up chest CT available for review (NCT 03730428). Serial chest CT scans were reviewed for abnormalities suspicious for DRP by an independent review of two radiologists. Log rank and Cox proportional hazards regression analysis were used for the time-to-event analysis. Results: DRP was radiographically detected in 45/86 patients (52.3%). Over 80% of DRP occurred in the first 4 months of treatment (cumulative risk 52.3%). Most patients with DRP were asymptomatic (n = 31, 68.9%). Among 14 patients with clinical manifestation, common symptoms included cough, fever and shortness of breath. DRP mostly distributed in bilateral lower lobes. Ground glass opacities and reticular opacities were seen in most of the cases. Elderly patients (OR 1.09, p = 0.002) and patients with baseline pneumonitis (OR 3.96, p = 0.023) are more likely to develop DRP. Patients who developed DRP had significantly longer progression free survival (median 6.8 vs 4.1 months, p = 0.024) and overall survival (OS, median 42.8 vs 21.3 months, p = 0.016). DRP was a predictor of improved OS by multivariate Cox analysis (HR 0.49, 95%CI 0.25-0.97, p = 0.040). Conclusions: DRP was noted in half of the MBC patients treated with EVE. Our preliminary data suggested that DRP would be a predictor for better outcome, which should be further investigated. Given the incidence and outcomes of patients with DRP, close monitoring, prompt diagnoses and appropriate treatment for DRP are critical for the preservation of patients’ quality of life and achievement of maximal treatment outcomes.