EVERSUN: A phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma

Davis, I. D., Long, A., Yip, S., Espinoza, D., Thompson, J. F., Kichenadasse, G., Harrison, M., Lowenthal, R. M., Pavlakis, N., Azad, A., Kannourakis, G., Steer, C., Goldstein, D., Shapiro, J., Harvie, R., Jovanovic, L., Hudson, A. L., Nelson, C. C., Stockler, M. R., & Martin, A. (2015) EVERSUN: A phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma. Annals of Oncology, 26(6), pp. 1118-1123.

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Abstract

Background

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).

Patients and methods

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.

Results

We recruited 55 eligible participants from September 2010 to August 2012. Demographics: 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.

Conclusions

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.

Impact and interest:

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3 citations in Web of Science®

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ID Code: 86616
Item Type: Journal Article
Refereed: Yes
Keywords: Carcinoma, Renal Cell, Clinical Trial, suntinib, everolimus, Angiogenesis Inhibitors, Receptors, Vascular Endothelial Growth Factor, MTOR protein, human
DOI: 10.1093/annonc/mdv078
ISSN: 1569-8041
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Therapy (excl. Chemotherapy and Radiation Therapy) (111204)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2015 The Author
Deposited On: 29 Oct 2015 02:01
Last Modified: 29 Oct 2015 21:57

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