Sequential use of sorafenib and sunitinib in advanced renal cell carcinoma: does the order of sequencing matter?

To investigate the sequential use of two tyrosine-kinase inhibitors (TKI), sorafenib (SOR) and sunitinib (SUN), in advanced renal carcinoma. We retrospectively analyzed the clinical outcome of 33 patients who had experienced progression or unacceptable toxicity after receiving either sorafenib or sunitinib and then switched to the other reciprocal agent. Progression-free survival (PFS) during the first TKI was similar regardless of drug with a median of 6 months in the SOR-SUN group (n = 15) and 7.5 months in the SUN-SOR group (n = 18). Interestingly, PFS during the second TKI was significantly longer in the SOR-SUN group as compared to the SUN-SOR group with median values of 11 and 3 months, respectively (P = 0.0377; HR 0.46; 95% CI: 0.16-0.95). As a consequence, total PFS (sum of PFS on first and second TKI) was significantly longer in the SOR-SUN group than in the SUN-SOR group with medians of 20 versus 10 months, respectively (P = 0.0393; HR 0.47; 95% CI: 0.18-0.96). Median wash-out period between the two TKI was 3 weeks in both groups. Differences in baseline characteristics, including histology and line of treatment, were not significant, and toxicity was not increased during the second part of the sequence. Here, we show that responses can be achieved when a second TKI is given soon after a TKI failure in renal cancer with apparent more durable disease control when SOR is followed by SUN.