Correlation of Stomatitis and Cutaneous Toxicity With Clinical Outcome in Patients With Metastatic Renal-Cell Carcinoma Treated With Everolimus

Abstract Background In clinical practice, discontinuation or dose reduction of everolimus may be induced not only by grade 3 or 4 toxicities but also by prolonged grade 2 toxicities, such as stomatitis and/or cutaneous toxicity, which share some pathogenetic mechanisms. We assessed the correlation between either everolimus discontinuation or dose reduction induced by stomatitis–cutaneous toxicity events (SCTE) and clinical outcome of patients with metastatic renal-cell cancer (mRCC). Patients and Methods We retrospectively reviewed the clinical data of patients with mRCC treated with everolimus in 2 Italian centers. Clinical evidence of SCTE was evaluated, and corresponding clinical data were reviewed for response and clinical outcome. Results Seventy-nine mRCC patients treated with everolimus (57 male, 22 female; median age 66 years; range, 44-88 years) were evaluated. SCTE were observed in 20 (25%) of 79 patients at a median of 30.5 days of everolimus treatment (range, 10-270 days). Partial response or stable disease was achieved in 15 (79%) of 19 evaluable patients with SCTE compared to 28 (48%) of 58 with no SCTE ( P  = .03). At a median follow-up of 19 months, a significant difference was found in the median PFS equal to 7.8 months (95% confidence interval [CI], 2.8-24.4) in SCTE patients versus 4.3 months (95% CI, 2.7-7.5) in non-SCTE patients ( P  = .029), and in the median OS equal to 30.6 months (95% CI, 19.6–not reached) in SCTE patients versus 13.5 months (95% CI, 9.9-17.7) in non-SCTE patients ( P  = .0007). Conclusion These data suggest that SCTE may be a predictive marker of favorable outcome in mRCC patients treated with everolimus.