ASCO 2017: Effects of pazopanib and sunitinib dose modification on safety and efficacy in patients with metastatic renal cell carcinoma from COMPARZ

Chicago, IL ( COMPARZ was a randomized, controlled, open-label, phase 3 trial that demonstrated comparable efficacy of first-line pazopanib (PAZ) and sunitinib (SUN), but favorable safety and quality of life profiles for PAZ in patients (pts) with metastatic renal cell carcinoma (mRCC).1 Dr. Bjarnason presented a study evaluating the relationship between dosing, safety, and efficacy in PAZ- and SUN-treated pts who did or did not undergo dose reduction or interruption resulting from adverse events (AEs) and other reasons.

The AEs and median progression-free survival (mPFS) of PAZ and SUN were evaluated for pts with no, any, 1, and ≥2 dose reductions or dose interruptions lasting ≥7 days.

The results showed similar percentages of pts in the PAZ and SUN groups having a dose interruption (44% vs 49%, respectively) or reduction (44% and 51%, respectively). The incidence of AEs in pts from the PAZ and SUN groups with dose modifications was higher compared to those with no dose modifications. Longer mPFS was observed in pts with dose modification, as can be seen in the table below. Pts treated with PAZ or SUN with no dose reductions had mPFS of 7.3 months (mos) and 5.5 mos, respectively, whereas pts with any dose reduction had mPFS of 12.5 mos and 13.8 mos, respectively. Similarly, pts treated with PAZ or SUN with no dose interruptions lasting ≥7 days had mPFS of 8.2 mos and 5.6 mos, respectively, whereas those with any dose interruption lasting ≥7 days had mPFS of 12.6 mos and 13.8 mos, respectively. Pts with 2 or more dose interruptions or reductions had mPFS > 16 mos with both SUN and PAZ.

In summary, consistent with previous data for SUN, the current analyses showed longer mPFS with PAZ and SUN when dose modification is required to manage toxicity, suggesting that pts are not disadvantaged by such dose reductions or interruptions. Dr. Bjarnson suggest that patients not requiring dose modification may have sub-optimal therapeutic drug exposure.

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Presented By: Georg A. Bjarnason, Sunnybrook Research Institute, Toronto, ON, Canada

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
Twitter: @GoldbergHanan

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA

1. Casper J, Schumann-Binarsch S, Kohne CH. Pazopanib versus sunitinib in renal cancer. The New England journal of medicine 2013; 369(20): 1969.