Mammalian target of rapamycin (mTOR) inhibitor‐associated non‐infectious pneumonitis in patients with renal cell cancer: predictors, management, and outcomes

Abstract

Objective To characterize the incidence, onset, management, predictors, and clinical impact of mTOR inhibitor associated noninfectious pneumonitis (NIP) on patients with metastatic renal cell carcinoma. Patients and methods Retrospective review of 310 patients with metastatic renal cell carcinoma who received temsirolimus and/or everolimus between 6/1/2007 and 10/1/2010. Clinical correlations were made with serial radiologic imaging. Fisher’s exact, Wilcoxon rank sum, and logistic regression analysis were performed to evaluate the association of NIP with demographic or clinical factors. Log rank and Cox proportional hazards regression analysis were used for the time-to-event analysis. Results NIP occurred in 6% of temsirolimus and 23% of everolimus treated patients. Symptoms included cough, dyspnea, and fever (median of two and three symptoms per patient, respectively). Median NCI-CTCAE pneumonitis grade was 2 for both groups. Older age and everolimus treatment were predictive of NIP. Patients who developed NIP had significantly longer time on treatment (median 4.1 months vs 2 months) and overall survival (OS) (median 15.4 months vs 7.4 months). NIP was a predictor of improved OS by multivariate analysis. Conclusions An increased incidence of NIP was observed in everolimus treated patients. Improved OS in patients who developed NIP is an intriguing finding and should be further investigated. Given the incidence, morbidity, and outcomes seen in patients on everolimus who develop NIP, management should include proactive monitoring and treatment of NIP with the goal of preserving mTOR inhibitor therapy.

Comparative effectiveness of second-line targeted therapies for metastatic renal cell carcinoma: synthesis of findings from two multi-practice chart reviews in the United States

“…[ 35 study raises concerns about the use of mTOR inhibitors in the second line setting, it is clear from studies comparing the toxicity profiles of everolimus and temsirolimus that the two agents are not interchangeable 36,37 . The results of the current study lend further credence to the possibility that the two mTOR inhibitors are indeed distinctly acting agents.…”

Relationship between Pulmonary Adverse Events and Everolimus Exposure in Japanese and Non-Japanese Patients: A Meta-Analysis of Oncology Trials

“…Although the mechanism of everolimus-induced pulmonary AEs is unknown, the involvement of cell-mediated autoimmune response and T-cell-mediated delayedtype hypersensitivity has been postulated as a potential mechanism [3,5,8] . Patients with a presumptive diagnosis of an everolimus-induced pulmonary AE should be evaluated by use of lung function tests, HRCT, BAL, diagnostic tests to exclude opportunistic infections (e.g., polyoma BK viral infections), and pulmonary biopsies to exclude carcinomatous lymphangitis or other causes of ILD [3] .…”

Interstitial Lung Disease Induced by Targeted Therapy for Non-Small Cell Lung Cancer: A Review of Diagnosis, Workup, and Management

“…Everolimus was used for the treatment of advanced RCC, and PNET. The frequencies of ILD related to everolimus ranged from 8 to 14% of treated patients [36][37][38][39][40][41][42]. The mortality rate due to ILD was reported to be 3.8% (4 of 105 patients) in a previous study [4].…”

“…Temsirolimus was used for the treatment of advanced RCC. Temsirolimus-associated ILD had been reported in 0.5 to 5 % of cancer patients in several studies, and the fatalities were rare [32][33][34][35][36]. Everolimus was used for the treatment of advanced RCC, and PNET.…”