By Lynda Williams, Senior medwireNews Reporter
Results for the RECORD-3 trial support the current strategy of first-line sunitinib followed by second-line everolimus for the treatment of patients with metastatic renal cell carcinoma (mRCC).
As explained in the Journal of Clinical Oncology, the phase II study researchers hypothesised that first-line everolimus followed by second-line sunitinib at the first sign of disease progression would be better tolerated than the reverse and would therefore offer patients better progression-free survival (PFS).
However, median PFS to the start of second-line treatment was significantly lower for the 238 patients who were randomly assigned to receive first-line everolimus than for the 233 patients given first-line sunitinib, at 7.9 versus 10.7 months and with a hazard ratio (HR) of 1.4.
This HR was above the prespecified value of 1.1 for the primary endpoint; the one-sided 90% confidence interval upper limit was 1.64, in excess of the prespecified margin of 1.27.
Thus, the study failed to show noninferiority for first-line everolimus versus first-line sunitinib, say Robert Motzer, from Memorial Sloan-Kettering Cancer Center in New York, USA, and co-authors.
“These clinically relevant differences support the standard treatment sequence, whereby patients who experience progression on (or are intolerant of) first-line sunitinib are subsequently treated with everolimus”, they write.
Overall, 45% of patients given first-line everolimus switched to second-line treatment, as did 43% of those given first-line sunitinib.
The median combined PFS was 21.1 months for patients given first-line everolimus then second-line sunitinib versus 25.8 months for first-line sunitinib followed by second-line everolimus; the difference was nonsignificant.
Median overall survival was 22.4 months for first-line everolimus and then second-line sunitinib and 32.0 months for first-line sunitinib then second-line everolimus, and again the difference between the treatment arms did not reach statistical significance.
Patients in the first-line everolimus and first-line sunitinib groups reported similar side effects, with stomatitis (53 and 57%), fatigue (45 and 51%), and diarrhoea (38 and 57%), the most common.
“The observed [adverse events] were consistent with the known safety profiles of everolimus and sunitinib and differentiated by their respective mTOR [mammalian target of rapamycin] inhibitor and VEGFR [vascular endothelial growth factor receptor] tyrosine kinase inhibitor class,” Motzer and team observe.
They conclude: “The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression”.
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