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Title: EVERSUN: a phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma.
Authors: Davis, I D;Long, A;Yip, S;Espinoza, D;Thompson, J F;Kichenadasse, G;Harrison, M;Lowenthal, R M;Pavlakis, N;Azad, Arun A;Kannourakis, G;Steer, C;Goldstein, D;Shapiro, J;Harvie, R;Jovanovic, L;Hudson, A L;Nelson, C C;Stockler, M R;Martin, A
Affiliation: Monash University Eastern Health Clinical School, Melbourne
NHMRC Clinical Trials Centre, University of Sydney, Sydney
Flinders Centre for Innovation in Cancer, Flinders University, Adelaide
Chris O'Brien Lifehouse, Royal Prince Alfred Hospital, Sydney Liverpool Hospital, Liverpool
Royal Hobart Hospital and Menzies Institute for Medical Research, University of Tasmania, Hobart
Royal North Shore Hospital, University of Sydney, Sydney
Austin Health, Heidelberg, Victoria, Australia
Ballarat Oncology & Haematology Services and Fiona Elsey Cancer Research Institute, Ballarat Federation University, Ballarat..
Border Medical Oncology, Wodonga
Prince of Wales Clinical School and Prince of Wales Hospital, University of New South Wales, Sydney
Cabrini Hospital, Melbourne
Bill Walsh Translational Cancer Research Laboratories, Kolling Institute, Sydney
Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane
ANZUP Cancer Trials Group, Sydney
Sydney Catalyst Translational Cancer Research Centre, University of Sydney, Sydney
Issue Date: Jun-2015
EDate: 2015-02-20
Citation: Annals of oncology : official journal of the European Society for Medical Oncology 2015; 26(6): 1118-1123
Abstract: We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. We recruited 55 eligible participants from September 2010 to August 2012. mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5-10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12-undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment. ACTRN12609000643279.
DOI: 10.1093/annonc/mdv078
PubMed URL: 25701452
Type: Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Subjects: angiogenesis inhibitors
clinical trial
renal cell carcinoma
vascular endothelial growth factor receptors
Appears in Collections:Journal articles

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