840P - Sequential Targeted Therapy Following Pazopanib (PZ) in Patients (PTS) with Metastatic Renal Cell Cancer (MRCC): Efficacy and Toxicity

Abstract

ABSTRACT Background The optimal sequence for a switch from pazopanib (PZ) to another targeted therapy (VEGF or mTOR inhibitor) is not yet defined. Recent findings suggest that the sequential use of anti-VEGF therapies may provide similar PFS (Progression Free Survival) benefit than mTOR inhibitors. We embarked on characterizing the clinical outcome to targeted therapies after the use of PZ from a multicenter retrospective study. Methods We reviewed the records of 36 pts with mRCC from 6 sites in Europe and US who received either a VEGF or an mTOR inhibitor after PZ. Pts and disease characteristics (demographic data, MSKCC and Heng prognostic score), disease outcome (objective response, PFS) and toxicity were compared between the two sequential treatment options. Results The median age was 62 (range 30–79) and 89% were males, mostly with clear-cell histology (97.2%) and good or intermediate MSKCC (97%) and Heng (93%) prognostic score. PZ was given as second line therapy after cytokines (n= 7) or sunitinib (n = 2) in 25% of pts, and as first line in 75%. Median PFS for PZ treatment was 9.3 months (mo) (CI 95%: 6,3–12,4 mo). Post- PZ therapies were: anti-VEGF in 23 patients (sorafenib n = 10, sunitinb n = 3, cediranib n = 4, cabozantinib n = 3 and bevacizumab n = 3) and mTOR inhibitors in 13 (everolimus (EV)). Median duration of post-PZ therapy was 6.2 mo in anti-VEGF and 2.6 mo in EV-treated pts (p = 0.017). Partial Response (PR) was only observed in 2 pts treated with anti-VEGF agents. Clinical benefit (PR+ Stable Disease) was observed in 80% and 33% of anti-VEGF and EV treated patients (p = 0.021). The most common Grade 1-2 adverse events (AE) were asthenia (50%), diarrhea (31,8%), Hand-foot syndrome (27%), rash (22,7%) and stomatitis (13,6%) for the anti-VEGF treated group; and asthenia (30,8%), respiratory toxicity (23%) and metabolic alterations (15,4%) for EV. Grade 3-4 AE occurred in 18% of anti-VEGF and 23% of EV groups. Median PFS was 7,3 mo for anti-VEGF and 2,4 mo for EV, with a HR of 0,36 (CI 95% 0.16 – 0.81; p = 0.014). Conclusions In this retrospective study, anti-VEGF therapy resulted in acceptable PFS benefit in post-PZ treated patients, and was well tolerated. These findings support the sequential use of an anti-VEGF in post PZ progression. The different type of anti-VEGF agents in this study is a major limitation. Disclosure All authors have declared no conflicts of interest.