Prognostic value of flare-up phenomenon after discontinuation of sunitinib (SU) or pazopanib (PA) in metastatic renal cell carcinoma (mRCC).

Abstract

448 Background: SU and PA are VEGFR inhibitors, approved for the treatment of mRCC. Cessation of treatment has been reported to induce flare-up, with increased tumor growth rate (TGR). We aimed to investigate this phenomenon and its prognostic role in mRCC. Methods: Patients who discontinued first line SU or PA with available data about CT scans performed before (t-1), at the time of discontinuation (t0) and after (t+1), were included in this analysis. TGR was evaluated as the difference between the sum of longest diameters (SLD) of the target lesions during the interval time between the CTs (TGR1=SLD0–SLD-1/t0-t-1 and TGR2=SLD+1-SLD0/t+1-t0) and expressed in cm/month. Flare-up was evaluated as the difference between the TGRs. Median overall survival was evaluated from t0 (OS0) to death by the Kaplan-Meier method and correlation with variables was evaluated with Cox model. Results: Sixty-three patients treated from Oct 2006 to Nov 2012 at the Institut Gustave Roussy were eligible. Median age was 57.1 y, 81% were males, 89% had SU and 11% PA. Heng prognostic groups were good in 33% and intermediate in 67% of the pts. Median OS0 was 24.1 months (95%CI, 8.3 – 40.0). Major reasons for discontinuation were durable partial/complete response (16%), severe toxicity (22%) and progression of disease (62%). The median TGR1 and TGR2 were 0.2 and 0.7 cm/month, respectively (p=0.001), no correlation was found (p=0.33) and no differences were found between SU and PA in TGR1 (p=0.95) and TGR2 (p=0.53). Median flare-up was 0.5 cm/month (IQR: 0.1 – 1.2); in pts who discontinued for response, toxicity, or PD it was 0.1 (IQR: -0.2 – 0.6), 0.5 (IQR; 0.2 – 2.0) and 0.8 (0.1 – 1.7), respectively. At the univariate analysis flare-up was a prognostic factor for OS0 (HR: 1.13, 95%CI: 1.02 – 1.24; p=0.018). When compared to Heng criteria in the multivariate analysis, it was confirmed to be an independent prognostic factor: each increase of 1 cm in flare-up increases the risk of death by 11% (HR: 1.11, 95%CI: 1.00 – 1.23; p=0.048). Conclusions: Flare-up is an independent prognostic factor present in patients affected by mRCC who discontinued SU or PA. This is independent by the reason for discontinuation and the type of therapy.