Everolimus-Associated Non-Infections Pneumonitis (NIP) in Korean Patients with Renal Cell Carcinoma (RCC)

Background Everolimus prolonged survival in advanced RCC patients who failed to VEGF inhibitors. However, nearly 13.5 to 30% of patients experienced NIP. Although a lower incidence of NIP was observed in Japanese patients from RECORD-1, the actual incidence of everolimus-associated NIP was unknown in Asian patients. Therefore, this study was undertaken to evaluate everolimus-associated NIP in Korean RCC patients treated with everolimus. Patients and methods Total 36 patients were enrolled at Seoul National University Hospital including advanced RCC patients who participated in REACT (N = 20) and in a trial for non-clear cell RCC (N = 16). NIP associated with everolimus was diagnosed using sequential computed tomography (CT) of the chest or bronchoscopy after an infectious origin and other causes of radiographic infiltrates were excluded. Clinico-pathologic findings were compared between NIP and non-NIP groups. Factors associated with NIP were identified using a binary logistic regression analysis. Results Overall, 10 (27.8%) of 36 RCC patients treated with everolimus developed NIP that was radiologically proven: ≥ grade 3, 6 (16.7%) patients; and grade 1, 4 (11.1%). Two patients died within 1 week after NIP diagnosis, while 8 recovered from NIP after cessation of everolimus (N = 4) and steroid use with drug interruption (N = 4). The mean cumulative dose of everolimus was 1,293 mg (range, 590-2420mg) at NIP diagnosis. There were no differences in NIP occurrence according to age, performance status, subtype (clear vs. non-clear), and underlying lung disease (Ps > .05). However, patients who experienced NIP had a better response (9 of 10 patients) than those without NIP (17 of 26) (P = .015). The response to everolimus remained predictive of NIP occurrence in multivariate analysis (P = .018). Conclusion NIP is relatively common (27.8%) in Korean patients with RCC who receive everolimus. Response to everolimus is an independent predictor for NIP development in advanced RCC patients. Disclosure All authors have declared no conflicts of interest.