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, 113 (3), 376-82

Mammalian Target of Rapamycin (mTOR) Inhibitor-Associated Non-Infectious Pneumonitis in Patients With Renal Cell Cancer: Predictors, Management, and Outcomes

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Mammalian Target of Rapamycin (mTOR) Inhibitor-Associated Non-Infectious Pneumonitis in Patients With Renal Cell Cancer: Predictors, Management, and Outcomes

Bradley J Atkinson et al. BJU Int.

Abstract

Objective: To characterise the incidence, onset, management, predictors, and clinical impact of mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis (NIP) on patients with metastatic renal cell carcinoma (mRCC).

Patients and methods: Retrospective review of 310 patients with mRCC who received temsirolimus and/or everolimus between June 2007 and October 2010. Clinical correlations were made with serial radiological imaging. Fisher's exact, Wilcoxon rank-sum, and logistic regression analyses were used to evaluate the association of NIP with demographic or clinical factors. Log-rank and Cox proportional hazards regression analyses were used for the time-to-event analysis.

Results: NIP occurred in 6% of temsirolimus-treated and 23% of everolimus-treated patients. Symptoms included cough, dyspnoea, and fever (median of two and three symptoms per patient, respectively). The median National Cancer Institute Common Toxicity Criteria for Adverse Events pneumonitis grade was 2 for both groups. Older age and everolimus treatment were predictive of NIP. Patients who developed NIP had a significantly longer time on treatment (median 4.1 vs 2 months) and overall survival (OS) (median 15.4 vs 7.4 months). NIP was a predictor of improved OS by multivariate analysis.

Conclusions: There was an increased incidence of NIP 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.

Keywords: everolimus; pneumonitis; renal cell carcinoma (RCC); temsirolimus.

Conflict of interest statement

Conflicts of Interest

Authors BA, DC, CN, RM, LX, and PC have no financial relationships to disclose. We attest that we have herein disclosed any and all financial or other relationships and that all sources of financial support for this study have been disclosed and are indicated.

Figures

Figure 1
Figure 1
CT chest radiographic charaterization of NIP. Patchy distribution of ground-glass opacities with interlobar septal thickening (1a. Note: also right pleural effusion), nonspecific area with ground-glass attenuation (1b. Note: lung metastasis in left lower lobe), and multifocal area of airspace consolidation (1c).
Figure 1
Figure 1
CT chest radiographic charaterization of NIP. Patchy distribution of ground-glass opacities with interlobar septal thickening (1a. Note: also right pleural effusion), nonspecific area with ground-glass attenuation (1b. Note: lung metastasis in left lower lobe), and multifocal area of airspace consolidation (1c).
Figure 1
Figure 1
CT chest radiographic charaterization of NIP. Patchy distribution of ground-glass opacities with interlobar septal thickening (1a. Note: also right pleural effusion), nonspecific area with ground-glass attenuation (1b. Note: lung metastasis in left lower lobe), and multifocal area of airspace consolidation (1c).
Figure 2
Figure 2
Association between noninfectious pneumonitis and Kaplan-Meier estimate for time on treatment (TOT).
Figure 3
Figure 3
Association between noninfectious pneumonitis and Kaplan-Meier estimate for overall survival (OS).

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