P0211 EVERSUN: A phase 2 trial of everolimus alternating with sunitinib as first-line therapy for advanced renal cell carcinoma (ANZUP Trial 0901)

• Published in: European journal of cancer (1990) Vol. 50; pp. e68 - e69
• Main Authors: Davis, I.D, Long, A, Martin, A, Espinoza, D, Yip, S, Thompson, J.F, Kichenadasse, G, Harrison, M, Lowenthal, R.M, Pavlakis, N, Azad, A, Kannourakis, G, Steer, C, Goldstein, D, Shapiro, J, Stockler, M.R
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.05.2014
• Subjects: Hematology, Oncology and Palliative Medicine
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2014.03.255

Background We hypothesised that alternating treatment with inhibitors of the VEGFR and mTOR pathways would delay the development of resistance in advanced renal cell carcinoma. Methods This was a single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of sunitinib 50 mg daily for 4 weeks on and 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on and 1 week off. Participants had advanced renal cell carcinoma categorised as Memorial Sloan-Kettering Cancer Center (MSKCC) good or intermediate risk. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints included feasibility, tumour response, overall survival (OS), and adverse events. Imaging was done every 6 weeks until week 24, then every 12 weeks. A planned sample size of 55 allowed distinction between a 6 month PFS rate of ⩽64% versus ⩾84% with type I and type II error rates of 5%. Findings We recruited 55 eligible participants, from September 2010 to August 2012; mean age was 61 years, 71% were male, 16% were in the favourable risk category, and 84% were intermediate risk. 80% of participants could start treatment cycle 2 within 14 weeks; 64% received ⩾22 weeks of alternating therapy and 78% received ⩾22 weeks of any treatment. 6 month PFS occurred in 29 of 55 participants (53%; 95% confidence interval [CI] 40–66). The overall response rate was seven of 55 (13%; 95% CI 4–22, all partial responses). After a median follow-up of 20 months, 47 of 55 participants had disease progression, with a median PFS of 8 months (95% CI 5–10), and 30 of 55 had died, with a median OS of 17 months (95% CI 12–undefined). Adverse events were consistent with those expected for each single agent. The most common grade 3 or 4 adverse events (by number of participants) were hypertension ( n = 13), anaemia ( n = 9), oral mucositis ( n = 7), fatigue ( n = 7), GGT increase ( n = 6), pain ( n = 5), and platelet count decrease ( n = 5). Interpretation The EVERSUN regimen was feasible and safe, but its activity did not meet prespecified values to warrant further research. This study supports the current approach of continuing first-line anti-VEGF therapy until progression or prohibitive toxicity before switching to another drug.