A phase II study of intermittent sunitinib (S) in previously untreated patients (pts) with metastatic renal cell carcinoma (mRCC).

Abstract

4515 Background: S as initial treatment in mRCC is limited by balancing acute and chronic toxicity with clinical benefit. Pre-clinical and retrospective clinical data support that extended treatment breaks are feasible without a reduction in efficacy. Methods: Pts with treatment-naïve clear cell mRCC were enrolled on a prospective phase II trial and initially treated with 4 cycles of S (50 mg 4/2). Pts with ≥ 10% reduction in tumor burden (TB) following 4 cycles had S held, with CT scans approximately every 10 weeks. S was re-initiated for 2 cycles in those pts with an increase in TB by ≥ 10% and again held with ≥ 10% TB reduction. This intermittent S dosing continued until RECIST-defined disease progression while on S. The primary objective was feasibility of intermittent S, defined as the proportion of eligible pts who underwent intermittent therapy. The alternative hypothesis was a feasibility of > 80% vs. a null hypothesis of < 50% (a=0.05; power 80%). Results: Thirty-six pts were enrolled; 70% male, median age 60, 95% PS 0/1 and 32% favorable/65% intermediate by Heng criteria. Twenty pts were eligible for intermittent therapy and all pts (100%) entered the intermittent phase. Pts were not eligible for intermittent S due to PD (n=13); toxicity (n=1) or w/d of consent (n=2) prior to end of cycle #4. Sixteen pts (80%) had ≥ 10% TB increase off S with a median (range) increase of 1.5 cm (1.1-2.5) compared to the TB immediately prior to stopping S, considering all off periods.Four pts did not have ≥ 10% TB increase off S (3 pts after the 1st off period; off for 12, 8 and 5 months to date and 1 pt after the 2nd off period; off for 8 months prior to restarting S). Most pts exhibited a stable saw tooth pattern of TB reduction on S and TB increase off S. No pt had RECIST-defined PD while on S, but 2 pts were taken off extended breaks due to gradual TB increase over time, and 1 pt developed new CNS mets during the 2nd off period.The objective response rate was 53%. Toxicity was typical for S and completely resolved during treatment breaks. Conclusions: S dosing with periodic extended time off drug is feasible and associated with reduction in toxicity during the off periods. Clinical efficacy does not appear to be compromised. Clinical trial information: NCT01158222.