A phase II trial of gefitinib and pegylated interferon alfa 2b (PEG-IFN) in previously-treated renal cell carcinoma (RCC)

Abstract

e16115 Background: Modulation of the epidermal growth factor receptor (EGFR) pathway is relevant to IFN activity in RCC. Cell lines sensitive to IFN's antiproliferative effects downregulate EGFR, while IFN treatment of resistant cells precludes such an effect. (Eisenkraft et al, Cancer Res. 1991) Lack of EGFR down-regulation may thus be responsible in part for IFN resistance. To explore this hypothesis, we conducted a trial of the EGFR tyrosine kinase inhibitor gefitinib plus PEG-IFN in RCC patients (pts). Methods: Unresectable or metastatic RCC pts (no limit on prior therapies; performance status 0–2, and adequate end-organ function) were eligible. Prior IFN was allowed. Dose schedule: PEG-IFN SQ weekly (6μg/kg/week or 4 μg/kg/week) × 12 weeks and gefitinib 250 mg po daily until progression. A 6-month progression free survival (PFS) rate of 50% was considered promising (vs. 30%) in a two-stage design incorporating the Green-Dahlberg rule. We accrued 21 patients in the first-stage of accrual. Results: Pt characteristics: Males -16; median age - 56 years; Prior nephrectomy - 12. All had > 1 prior systemic therapy . Accrual slowed with increased use of small molecule kinase inhibitors, bevacizumab, and temsirolimus for RCC. At 6 months, PFS was 26% (95% CI: 9%, 49%); 20% (4 pts) had died. Best responses by RECIST: complete (1), partial (4), stable (8); progression (4). Response duration: CR (35+ months) and PR (3, 5, 5, 38+ months). Median time to treatment failure was 18.4 weeks (95%CI: 7.4, 24.9). Median PFS and overall survival were 23 and 53 weeks, respectively. Most common treatment-related toxicities were leucopenia, thrombocytopenia, rash, nausea, diarrhea, and hyperglycemia. Conclusions: Although gefitinib plus PEG-IFN did not meet the pre-specified 6-month PFS of 50%, it appears to have activity similar to other first-line therapies even in this previously-treated setting. (Supported by Astra Zeneca) [Table: see text]