820P - Sunitinib (2 weeks on/1 week off schedule) in metastatic renal cell cancer patients. Progression free and overall survival

Abstract

The recommended schedule of sunitinib (SU) for metastatic renal cell cancer (mRCC) pts is 50 mg/day p.o. for 4 weeks and 2 weeks rest. The half-life of SU and its active metabolite is very slow: 40-60 and 80-110 hours, respectively. Given on several consecutive days the accumulation is 3-4-fold and 7-10-fold, respectively. The steady state concentration is achieved on days 7-10 and 10-14. 50 mg daily is enough to achieve the target concentration of ≥ 50 ng/mL. During the 14 days rest the concentration will decrease to the starting level. The correlation between the SU AUC and the time to progression is well known. Based on the above in case of short term adverse events (AEs) we have applied the 2 weeks on/1 week off schedule instead of dose reduction. Altogether 130 mRCC pts (median age: 61 yrs, M/F: 91/39) were enrolled in the study. 121 (93%) pts were nephrectomized, 95% (123pts) had RCC histology. 67 (30%); 49 (38%) and 42 (32%) pts belongs to the good, intermediate and poor MSKCC prognostic groups, respectively. SU was the first-line treatment in 75 cases (58%), 34 (26%) had IFN and 21 (16%) patients had IL-2 treatment before. Patients received altogether 1617 cycles of SU (median 8, range: 1-68); 344 (range1-56) cycles were given according to 4/2, and 1273 (1-18) according to 2/1 schedule, respectively. Upon progression on SU the following therapies were given: sorafenib (n = 10), axitinib (7), pazopanib (1), cabozantinib (1), everolimus (16). The median progression-free survival (mPFS) was: 13.5 (95%CI 12-16.5) mos and the median overall survival (mOS) was 30 (24-36) mos. If the 2/1 schedule was given in more than 2/3 of the total cycles (n = 83) the mPFS was 18 (13.5-28.5) mos and mOS was 38 (30-44) mos compared to those who had 2/1 schedule in less than 2/3 of the total cycles (n = 47) with mPFS 6 (4.5-9; P = .0002) mos and mOS 11 (7-21); P = .0001) mos. Short-term AEs were as follows: fatigue 41%; anorexia 25%; mucositis 35%, diarrhea 37%; hand-foot syndrome 35%; hypertension: 30%. Although the AEs were quite frequent they lasted shorter and dose reduction had to be performed only in 12% (n = 16) during the 2/1 schedule. Changing the SU 4/2 to 2/1 schedule instead of reducing the dose, was safe and resulted in a longer median progression-free and overall survival.