CHICAGO—Individualizing first-line sunitinib is “safe and feasible” and was associated with improved response and survival times among patients with metastatic renal cell carcinoma (RCC), according to results (abstract 4514) from a multicenter phase II trial presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6.
“It is evident that there exists no magic ‘one size fits all’ dose approach,” commented Viktor Grünwald, MD, of Medical School Hannover in Germany, who presented the results. The study supported individualized dosing but the role of dose escalation per se remains “less clear,” he cautioned.
Some patients will require additional regimen adaptation to individualize dose schedules, reported lead study author Georg A. Bjarnason, MD, of the Sunnybrook Research Institute in Toronto, and colleagues.
Because higher sunitinib exposure has been shown to improve patient outcomes, the researchers enrolled 117 patients in the study to assess whether or not toxicity-driven dose escalation and dose/schedule individualization improved progression-free survival.
Nine non-evaluable patients discontinued treatment because of toxicity (n = 5), noncompliance (n = 2), or global deterioration (n = 2), Bjarnason noted. Of the 108 remaining response-evaluable patients, 10 remained on treatment at the time of analysis.
After 50 mg daily for 28 days, the dose was escalated for patients with minimal toxicity. Of the 36 patients who had a dose escalation to 62.5 mg, 6 patients maintained that dose, 18 patients went on to a second dose escalation to 75 mg, and 12 patients had a dose reduction (dose was reduced to 50 mg for 9 patients and to < 50 mg for 3 patients).
Ten (56%) patients who were dose-escalated to 75 mg had to undergo subsequent dose reductions. Eight maintained the 75-mg dose.
Together, dose reductions at the 62.5-mg and 75-mg levels represented 61% of the study participants who had undergone dose escalation, noted Grünwald. That raises questions about dose escalation, but along with survival time findings, bolsters the idea of sunitinib dose individualization, he said.
Three patients (2.8%) experienced complete response and 51 (47%) experienced partial response, compared with 0% and 32% in historical outcomes from the EFFECT clinical trial. Including stable disease, the objective response rate was 90.7% compared with 75% in the EFFECT trial.
At a median follow-up of 15.5 months, progression-free survival was 11.9 months (9.3–16.5 months), compared with a historical progression-free survival of 8.5 months (6.9–11.1 months) in the EFFECT trial. Overall survival was 35.9 months (27.4 months–not reached) vs 23.1 months (17.4–25.4 months), respectively.