Clinical management and resolution of stomatitis in BOLERO-2.

Abstract

558 Background: In BOLERO-2, adding everolimus (EVE) to exemestane (EXE) more than doubled progression-free survival without affecting quality of life vs EXE alone in postmenopausal women with hormone-receptor–positive advanced breast cancer who had recurrence or progression on/after nonsteroidal aromatase inhibitor therapy. Although mTOR inhibitors are generally well tolerated, stomatitis is one of their most clinically relevant and potentially dose-limiting toxicities (Sonis Cancer2010). The incidence, grade, and clinical course of stomatitis among patients (pts) participating in the BOLERO-2 study are described. Methods: Pts were randomized 2:1 to receive EVE+EXE or placebo (PBO)+EXE. Stomatitis incidence, severity, consequent dose interruptions/adjustments, study drug discontinuations, and time to resolution were recorded. Results: The median duration of EVE+EXE treatment exposure was 30 wk (range, 1-123 wk). Stomatitis (any grade) occurred more frequently with EVE+EXE than with PBO+EXE (59% vs 12%, respectively). Grade 3 stomatitis occurred in 8% vs 1% of pts receiving EVE+EXE vs PBO+EXE, respectively; no grade 4 was reported. Onset of grade ≥2 stomatitis after treatment initiation was earlier in the EVE+EXE arm vs the PBO+EXE arm: median time was 15d vs 24d, respectively. In the EVE+EXE arm, 97% of pts with grade 3 stomatitis (n=38) improved to ≤1 after a median of 13 d. Complete resolution was observed in 82% of these pts after a median of 38 d. In the PBO+EXE arm, all pts with grade 3 stomatitis (n=2) improved to ≤1 after a median of 18 d. Complete resolution was observed after a median of 29 d. Overall, 24% of pts in the EVE+EXE arm required dose interruptions/adjustments vs 1% of pts in the PBO+EXE arm, and 3% of pts (n=13) discontinued EVE+EXE vs <1% of pts (n=1) discontinuing PBO+EXE, all related to stomatitis. Conclusions: The BOLERO-2 data foster a new era of combining targeted and endocrine therapies. In the study, treatment-emergent stomatitis was of mild to moderate intensity, occurred shortly after treatment initiation, and was generally reversible. Most incidents were successfully managed with palliative interventions and temporary dose modifications. Oral hygiene and other preventive measures are recommended. Clinical trial information: NCT00863655.