e15071 Background: Second-line chemotherapy after docetaxel-based regimens for mHRPC remains undefined. Epithelial growth factor receptor (EGFR) expression is increased in prostate cancer. Clinical trials evaluating EGFR inhibitors as monotherapy have generally rendered little clinical benefit. In vitro studies demonstrated synergy by combining gefitinib with chemotherapy agents in prostate cancer cell lines. Based on these results, we conducted a phase II study with the aim of evaluating the clinical benefit of gefitinib with etoposide in patients with mHRPC after docetaxel-based therapy. Methods: Eligibility requirements included mHRPC with progression after docetaxel-based therapy, ECOG 0/1 and adequate organ function. A 3-week cycle included gefitinib 250 mg/d PO continuous with etoposide 50 mg/m2/d PO (rounded to 50 mg tablet) days 1-14. Toxicity was assessed every cycle and restaging occurred every 2 cycles. Reasons for terminating patient participation included toxicity, disease progression (per PSAWG 1) or voluntary withdrawal. Results: Twenty-four subjects were enrolled. Baseline characteristics are listed in the table. Median cycles per subject: 2 (range, <1–12). There were no PSA or objective responses. Nine patients (37%) were not evaluable for response: voluntary withdrawal (n=7), seizures unrelated to study drug (n=1) and development of a second malignancy (n=1). Stable disease was noted in 4/15 evaluable subjects (27%). The probability of progression free survival and overall survival at 1 year was 26% (10%-45%) and 44% (21%-65%) respectively, with a median survival of 11.3 months (range, 5.6 – 45.2) for all subjects. Grade 3 or 4 toxicities with >10% incidence included anemia (25%) and weakness (13%). Conclusions: Gefitinib with etoposide is well tolerated by patients with mHRPC. Although no responses were observed, the progression free survival and overall survival were better than in single agent gefitinib studies suggesting clinical benefit which merits further study. Characteristic Median Range Age 71.5 yrs 48–81 yrs ECOG PS 0/1 – 9/15 Prior chemotherapy 2 1–6 Gleason 8 4–9 PSA at entry 230 29–4,502 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca