PFS Benefits With Sunitinib Versus Everolimus In Metastatic Non-Clear Cell RCC

Compared with everolimus, sunitinib extends radiographic progression-free survival in patients with metastatic non-clear cell renal cell carcinoma, but outcomes vary according to histological subtypes and risk groups

medwireNews: Patients with metastatic non-clear cell renal cell carcinoma (RCC) derive a significant progression-free survival (PFS) benefit with first-line sunitinib compared with everolimus , according to the phase II ASPEN trial.

However, the researchers report “substantial heterogeneity in outcomes by histology and prognostic risk groups” and suggest that these factors be considered when making the therapeutic choice between the tyrosine kinase inhibitor sunitinib and the mammalian target of rapamycin (mTOR) blocker everolimus.

Radiographic PFS was a median of 8.3 months for the 51 patients with metastatic non-clear cell RCC who were randomly assigned to receive open-label sunitinib 50 mg/day on a 4-weeks on, 2-weeks off schedule as initial therapy.

This compared with a median PFS of 5.6 months for their 57 counterparts who received everolimus 10 mg/day – a difference that met the predefined level of statistical significance for the study, says the team led by Andrew Armstrong, from Duke University and the Duke Cancer Institute in Durham, North Carolina, USA.

When patients were stratified by histology, those with papillary and unclassified non-clear cell RCC had longer median PFS with sunitinib than with everolimus (8.1 vs 5.5 and 11.5 vs 5.7 months, respectively), while patients with chromophobe histology derived a greater PFS benefit with everolimus than sunitinib (11.4 vs 5.5 months).

Similarly, sunitinib treatment prolonged PFS relative to everolimus in patients categorised as good or intermediate risk according to the Memorial Sloan Kettering Cancer Center (14.0 vs 5.7 and 6.5 vs 4.9 months, respectively), but not in those in the poor-risk subgroup (4.0 vs 6.1 months).

The investigators caution that the subgroup analyses were exploratory and non-powered, and warrant further confirmation in larger trials or meta-analyses.

But they nonetheless write inThe Lancet Oncology: “To some extent, these findings validate our molecular understandings of these disparate diseases, particularly in the case of chromophobe renal cell carcinoma, in which alterations in the PTEN-PI3K-AKT signal transduction pathway have been described and might predispose to downstream inhibition through mTOR.”

Overall, adverse events of grade 3 or 4 were observed in 78% of sunitinib-treated patients and 60% of those given everolimus. The most common of these was hypertension, occurring in 24% of patients in the sunitinib arm versus 2% in the everolimus arm, followed by infection (12 vs 7%) and diarrhoea (10 vs 2%).

By contrast, grade 3 or 4 stomatitis and pneumonitis were less frequent in the sunitinib compared with the everolimus group (0 vs 9% for each).

But Andrew Armstrong et al say that “no unexpected toxic effects” were reported for either agent.


Armstrong AJ, Halabi S, Eisen T,et al.Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial.Lancet Oncol 2016; Advance online publication 12 January. doi:

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