839P - Phase Ii Study of Individualized Sunitinib As First-Line Therapy for Metastatic Clear Cell Renal Cell Cancer (Mrcc)

Abstract

ABSTRACT Aim: A high sunitinib area under the curve is associated with more toxicity, and a better response rate (RR), progression free (PFS) and overall survival (OS). Retrospective data (Urol Oncol 2014;32:480) show poorer PFS and OS in mRCC patients (pts) with minimum toxicity on the standard 28 day (d)/14 d schedule vs. pts with toxicity leading to schedule and/or dose changes. We hypothesized that toxicity (mucositis, diarrhea, hand foot syndrome, fatigue, hematological) could serve as a surrogate to individualize therapy (Rx) to optimize drug exposure and manage toxicity for each pt. Methods: A prospective phase II study (same eligibility criteria as EFFECT trial) will enter 110 pts with the primary endpoint of improving PFS from 8.5 (EFFECT) to 14 Months. Pts start on a 50 mg dose with the intent to treat for 28 d with the Rx break reduced to 7 d for all Rx schedules. Pts with grade-2 toxicity by d 28 stay on the 28 d schedule. Patients with > grade-2 toxicity on d 28 on the first course continue Rx on a 50 mg dose with the number of d on Rx individually reduced aiming for ≤ grade-2 toxicity. Dose is reduced to 37.5 mg in pts that cannot tolerate 50 mg for at least 7 d and to 25 mg in pts that cannot tolerate 37.5 mg for at least 7 d with individualized duration of Rx based on toxicity. Pts with minimum toxicity on d 28 on the first course are dose escalated to 62.5 mg and then 75 mg on a 14 d /7 d schedule. Results: With 73 pts on study, dose and schedule data are available for 69 pts with 13 pts (18.8%) dose escalated to 62.5 mg (9 pts) and 75 mg (4 pts). In 33 pts (47.8%), that would have been dose reduced by standard criteria, a 50 mg dose was continued but for fewer d (7-16 d) and 13 pts (18.8%) stayed on a 28d/7d schedule. Dose was reduced to 37.5 mg in 6 pts (8.7% vs. 36 - 63% in 4 large trials) and to 25 mg in 4 pts (5.8 % vs. 15 - 19% in 4 trials). Rx was discontinued due to toxicity in 3 pts (4.3% vs. 15-19% in 4 trials). In 61 evaluable pts, we found complete responses (CR) in 3 pts, partial responses (PR) in 27 pts, stable disease (SD) > 3 months in 23 pts ( Conclusions: Individualized sunitinib dosing is safe and feasible in a multicenter setting and associated with improved dose intensity and a good response rate. Disclosure: G.A. Bjarnason: Pfizer - membership on an advisory board - Pfzer-sponsored research - Support to attend meetings; B. Naveen, C. Canil, S. North, D. Heng, P. Zalewski, D. Soulieres, D.J. Ruether, M.N. Reaume and A. Kapoor: Pfizer member on advisory boards; P. Venner: Pfizer member on advisory boards and sponsored research; C.K. Kollmannsberger: Pfizer membership on an advisory board; B.J. Eigl: Pfizer: consultancy, honoraria, research funding; J. Knox: Pfizer grant support. All other authors have declared no conflicts of interest.