Changes of pulmonary function test and development of non-infectious pneumonitis in patients with metastatic renal cell carcinoma treated with everolimus.
530 Background: The aim of this study was to evaluate the changes of pulmonary function test (PFT) during everolimus treatment and to assess whether the change of PFT is associated with the development of non-infectious pneumonitis in patients with metastatic renal cell carcinoma. In addition, we tried to determine whether everolimus-associated pneumonitis could affect the efficacy of everolimus. Methods: Patients with mRCC who had received everolimus (10 mg dose once daily) after failure to VEGF-TKI treatment and underwent baseline PFT with regular PFT follow up were included in this study. The diffusing capacity divided by the alveolar volume (DLCO/VA) was used among various parameters of PFT. Repeated-measures ANOVA was used to describe changes of DLCO/VA. A Cox proportional hazard model with pneumonitis onset as a time-dependent covariate used to assess the prognostic role of pneumonitis. Results: This study included 36 patients. Nine patients (30%) developed everolimus-associated pneumonitis (pneumonitis group) and 27 were included in non-pneumonitis group. Five patients (14%) among pnemonitis group were symptomatic. The baseline DLCO/VA of patients was 90.0%. It decreased to 80.2%, 76.4%, 76.0%, and 72.1% after everolimus treatment of 6, 12, 18, and 24 weeks, respectively. DLCO/VA declined significantly as the treatment duration becomes longer (p < 0.001). There was no significant difference in change of DLCO/VA between patients with pneumonitis and those without pneumonitis (p =0.435). On time-variant Cox analysis, the decrease of DLCO/VA was not correlated with the efficacy of everolimus in terms of progression free survival (PFS, HR=1.0, p=0.94) and overall survival (OS, HR=0.98, p=0.18), while development of pneumonitis was associated with poor PFS (HR=4.60, p=0.005). Conclusions: Although the eveolimus treatment decreased DLCO/VA, the decline of DLCO/VA was not associated with the development of pneumonitis. Changes in DLCO/VA were not related with efficacy of everolimus, while the development of pneumonitis was a prognostic factor for PFS.