Pegylated Interferon Alpha-2b (Peg-Intron) For Metastatic Renal Cell Cancer (Mrcc): Results Of A Phase Ii Clinical Trial And Biologic Correlates Of Response.

4528 Background: PEG-Intron (PEG-I) is a pegylated derivative of interferon alpha-2b (IFN), recombinant, with a single molecule of mono methoxy polyethylene glycol which increases serum half-life. Methods: A single arm, one-stage phase II trial was conducted between 6/02 and 6/04 in 32 previously untreated patients (pts) with mRCC to assess time to progression and biologic correlates (primary and secondary endpoints). Eligibility included measurable disease and fresh tumor procured at surgery for genetic and immunohistochemical (vascular endothelial growth factor [VEGF] and carbonic anhydrase IX [CAIX]) studies. PEG-I was given SC at a weekly dose of 4.5 μg/kg until progression or intolerability. Quality of life (QOL) was assessed using the FACT-BRM. Results: All 32 were evaluable, 91% had prior nephrectomy, and MSKCC risk group (JCO 20:289–96, 2002) was: 41% good, 53% intermediate, 6% poor. 10 pts (31%; 95% CI: 16%-50%) achieved a partial response (PR). Median time to progression was 5.0 mos (95% C.I. [3, 7]); median survival was 31 mos (95% C.I. [18, not reached]). There were no grade IV toxicities; primary grade III toxicities were hematologic (6/32 pts; 19%) and fatigue (4/32 pts; 13%). FACT-BRM scores showed an initial decrease in QOL at 2 weeks followed by partial recovery. Genomic profiling of tumor samples identified four novel genes that correlated with IFN resistance: ABCD3, Hs.76704, Hs.11325, and Hs.94122. Change in serum VEGF levels did not correlate with response. Tumor tissue samples are being immunohistochemically stained for CAIX. Conclusions: PEG-I treatment results in a 31% response rate and similar median time to progression as standard IFN (JCO 18:2972–80, 2000) in this population with predominantly good and intermediate risk pts. Once weekly dosing was generally well tolerated. Future investigation of PEG-I in combination with novel targeted agents in mRCC is warranted. Further study of the four identified genes may provide insight into IFN resistance. Supported by Schering-Plough, Inc. [Table: see text]