A phase II trial of sunitinib (S) in previously-treated pancreas adenocarcinoma (PAC), CALGB 80603

Abstract

4515 Background: S is an oral broad-spectrum tyrosine kinase (TK) inhibitor with potential utility in PAC given the perturbation of multiple signaling pathways and stromal alterations noted in PAC. CALGB conducted an NCI-sponsored phase II study of S in patients (pts) with previously-treated PAC. Methods: Eligibility included: PAC previously treated with front-line gemcitabine (gem) therapy, or progression of disease (PD) during or within 3-months of completion of adjuvant therapy, or newly metastatic disease following therapy for locally advanced PAC; performance status 0–2; measurable disease by RECIST; no prior anti-VEGF therapy; no evidence of duodenal invasion on CT. S was dosed at 50 mg daily for 28 days followed by 14 days of rest (1 cycle). Re-staging was performed after each of the first 4 cycles of therapy. Study design: Single-arm, multi-center cooperative group, 3-stage design, with response criteria of at least stable disease (SD) in 1/19, 2/39, for expansion. Planned accrual was 64. Primary endpoint: Response rate (RECIST). Secondary endpoints: Duration of response, toxicity, PFS, and survival. Results: From 11/06 to 11/07, 77 pts were accrued with the criteria met for full accrual (1 withdrew consent). Pt characteristics were: male 54%, female 46%, age: median 65 yrs, range 42- 87, and PS 0/1/2 45%/48%/7%. Prior therapy included: gem 61%, gem-based combination 37%, TK inhibitor 14%, radiation therapy 14%. Sites of disease were: liver 84%, lung 30%, other 19%. As of 12/07, 52 pts are evaluable for response. Response criteria for continuation were met at the two interim analyses. SD occurred in 7 pts [13%, 95% CI (3.6%, 22%)] and PD in 29 (56%). Number of cycles received was: 1- 86%; 2- 12%, 3- 2%. Dose modification was needed in 21%. Median PFS was 41 days (CI 37–57d), and median OS 97 days (CI 79–127d). Grade 3–5 toxicities included: hematologic 13% (G3), fatigue 12%, bleeding 6% (G3), nausea 4% (G3), Thrombosis/embolism 2% (G3), TTP/renal failure 2%, GI perforation 2% (G5). Conclusions: Preliminary analysis of a large cooperative group phase II study of S in previously-treated PAC suggests modest single agent activity and no new safety signals in this patient population. Final results will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer