Sorafenib (SOR) in patients (pts) with advanced/recurrent uterine carcinoma (UCA) or carcinosarcoma (CS): A phase II trial of the University of Chicago, PMH, and California Phase II Consortia

Abstract

5585 Background: There is no effective treatment for UCA/CS pts who have progressed on platinum-taxane therapy. Increased levels of VEGF are frequently seen in UCA and CS, and antiangiogenic therapy has shown activity in a mouse model of UCA. Sorafenib is a multitargeted kinase inhibitor with antiangiogenic activity that is approved for use in renal and hepatocellular carcinoma. Methods: We initiated a multi-center phase II trial of SOR in pts with advanced/recurrent UCA (arm A) or CS (arm B) and 0–1 prior chemotherapy regimens. PS 0–2 and measurable disease were required. The starting SOR dose was 400 mg orally twice daily. The primary endpoint was objective response, which was evaluated every 8 weeks. The trial design required 1 response in the first 12 evaluable pts to proceed to second stage. Results: 55 pts (39 UCA, 16 CS) enrolled between 3/05 and 10/07. Pt characteristics arm A: median age 65 (range 44- 83); PS 0/1/2: 16/19/3. Pt characteristics arm B: median age 64 (range 40- 87); PS 0/1/2: 7/8/1. Median number of four week SOR cycles administered in arm A = 3, (range 1–30; 11 pts remain on therapy) and in arm B= 2, (range 1–14; 2 pts remain on therapy). Selected grade 3/4 toxicities were: hypertension 13%, hand-foot syndrome 13%, hypophosphatemia 8%, anemia 6%, rash/desquamation 4%, diarrhea 4%, thrombosis 4%, fatigue 2%, bleeding 2%. Forty percent of pts required dose reduction. In arm A 2 pts (5%) had a partial response (PR), and 19 pts (50%) had stable disease (SD) after 2 months (mo) of therapy (11% at 4 mo). Median progression-free survival (PFS) was 3.4 mo (95% CI: 2.8–4.5), and median overall survival was 10.1 mo (95% CI: 6.9- not yet reached). In arm B 0 pts had PR and 4 pts (27%) had SD, median PFS was 2.3 mo (95% CI: 1.8- not yet reached),and median overall survival was 5.6 mo (95% CI: 2.2–17.6). Conclusions: These preliminary data suggest that SOR results in clinical benefit for a minority of UCA patients. Supported by N01-CM-17102 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer