MTOR inhibitor-associated noninfectious pneumonitis in patients with metastatic renal cell cancer: A single-center experience.

Abstract

e15612 Background: Noninfectious pneumonitis (NIP) is a known adverse effect of mTOR inhibitors, with a reported incidence of 25-45%. The goal of this review was to characterize the incidence, onset, management, and clinical outcomes of pts with mRCC who experienced mTOR inhibitor-associated NIP at our tertiary cancer center. Methods: Retrospective review of 310 mRCC pts who received everolimus and/or temsirolimus between 6/1/2007 and 10/1/2010. Clinical correlation was made in conjunction with serial radiologic imaging studies. Results: 36 mRCC pts (12%) treated with an mTOR inhibitor developed NIP with a median time to symptom onset of 65 d (21-855) and radiographic appearance of 62.5 d (35-736). 23 pts (21%) received everolimus compared to 13 pts (6%) who received temsirolimus (P<0.0001). Median time to onset, radiographic appearance, and NCI CTCAE pneumonitis grade did not differ significantly between treatments (P=NS). Increased age (OR 1.04; 95% CI: 1.004-1.08) and everolimus (OR 4.106; 95% CI: 1.96-8.6) were associated with a greater risk of NIP. NCI CTCAE grade 2 NIP severity was most common (78%). mTOR inhibitor therapy was discontinued in 9 pts (25%); continued at same dose in 7 pts (19%), dose reduced in 2 pts (6%); held and resumed at lower dose in 2 pts (6%), and held and then resumed at same dose in 1 pt (3%). Median time on treatment was greater for pts who developed NIP; 4.1 vs 2 mo (P=0.035). Median OS was significantly greater for NIP pts; 15.4 vs 7.4 mo (P<0.0001). 3-yr survival of NIP pts was 35.4% vs 7.2% (P<0.0001). Predictors of improved OS included NIP (HR 0.315; 95% CI: 0.2-0.495; P<0.0001). Conclusions: A higher incidence of NIP was observed in mRCC pts treated with everolimus than temsirolimus. The finding of improved OS in pts who developed NIP is intriguing and should be further investigated.