Sunitinib versus everolimus trial highlights non-clear cell RCC patient response heterogeneity

Jan 22 2016

By Lynda Williams, Senior medwireNews Reporter

Sunitinib offers significantly longer progression-free survival (PFS) than everolimus for patients with metastatic non-clear cell renal cell carcinoma (RCC), phase II trial results indicate, but treatment effect appears to depend upon key patient characteristics.

“Based on the present study and previous clinical studies, decisions on therapeutic choice between sunitinib and everolimus for patients with metastatic non-clear cell [RCC] should be based on prognostic risk criteria, histological subtype, and the known, expected side-effects”, say Andrew Armstrong, from Duke University in Durham, North Carolina, USA, and co-workers.

“Future clinical trials in these patients should also consider this heterogeneity of outcome when assessing novel agents”, they recommend in The Lancet Oncology. PFS was 8.3 months for the 51 patients randomly assigned to receive open-label, 6-week cycles of treatment with the VEGF receptor inhibitor sunitinib 50 mg/day compared with 5.6 months for the 57 patients given the mTOR inhibitor everolimus 10 mg/day, giving a significant hazard ratio (HR) of 1.41.

Exploratory forest plot analysis estimated, with an 80% confidence interval (CI), that PFS was higher with sunitinib for patients with a good or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk prognosis, with HRs of 2.9 and 1.4, respectively, whereas everolimus was favoured for those with a poor prognosis, with an HR of 0.3.

Similarly, patients with papillary histology had higher PFS when given sunitinib (HR=1.6), as did those with unclassified histology (HR=1.9), while those with chromophobe histology had an HR of 0.7 in favour of everolimus.

By contrast, PFS favoured sunitinib regardless of whether patient lactase dehydrogenase was elevated at baseline or not.

The researchers note that the small numbers of patients in the study meant that interactions between treatment subgroups could not be tested but believe that the results “provide reasonable estimates” of effect sizes by MSKCC prognosis and histology.

“Although a larger confirmatory study is needed to estimate the treatment effect with a tighter CI, these results offer the most definitive evidence to date supporting not only the heterogeneity of this disease and outcomes, but also that responses and outcomes to either an mTOR inhibitor-based or VEGF tyrosine kinase inhibitor-based approach depend on the specific groups”, the team emphasizes.

Overall survival was longer in sunitinib-treated patients than those given everolimus, at 31.5 versus 13.2 months, but the difference did not reach significance. Nor did subgroup analysis find a significant difference in the treatment groups by histology or prognostic risk.

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