ORLANDO—Patients with metastatic renal cell carcincoma (RCC) who develop hand-foot syndrome (HFS) while being treated with sunitinib may have better progression-free survival and overall survival than those who do not experience HFS, a recent analysis suggests.

“These findings are important because it would be of great interest to determine whether there are predictive biomarkers both before patients start therapy but also when patients are on therapy to help us figure out who are the patients who are going to benefit,” said lead investigator Dror Michaelson, MD, Assistant Professor of Medicine at Harvard Medical School in Boston. “We think if you don’t have this side effect [HFS], you don’t do as well as if you do have this side effect.”

Dr. Michaelson, who presented the study findings at the Fourth Annual Genitourinary Cancers Symposium, said HFS and related skin toxicities are common adverse effects of tyrosine kinase inhibitors such as sunitinib. An oral agent, sunitinib has been shown in a randomized phase 3 trial to provide superior progression-free survival to interferon-alpha (11 vs. 5 months) as first-line metastatic RCC therapy.

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In the current analysis, researchers examined correlations between sunitinib-associated HFS and efficacy endpoints in five clinical trials involving patients with metastatic RCC who receive first- or second-line treatment with sunitinib. The analyses included pooled data from 770 patients who received sunitinib at a dosage of 50 mg a day on a four-week-on/two-week-off schedule (544 patients, 71%) or 37.5 mg a day continuous dosing (226 patients, 29%). 

HFS developed in 179 patients (23%)FS and 591 patients (77%) did not develop HFS.  Most instances of HFS (63%) initially occurred during the first three treatment cycles. Dr.

PFS and OS were 14.3 months and 38.3 months, respectively, in the HFS group compared with 8.3 months and 18.9 months in the patients who did not develop HFS. Multivariate analysis showed that sunitinib-related HFS remained a significant independent predictor of both PFS and OS.

“One thing to consider based on these findings is that patients who develop this side effect shouldn’t be removed from treatment,” Dr. Michaelson said. “Every effort should be made to keep them on treatment and to manage toxicity because in fact they may ultimately do very well as far as their cancer control is concerned. We are not entirely sure why there is this correlation.  It could be a sign or marker of pharmacodynamics. So patients who develop HFS may have a higher drug exposure and their body is absorbing the drug better and that is why they are developing both the side effects and the clinical efficacy.”