A randomized phase II study of BAY 43-9006 in combination with gemcitabine in metastatic pancreatic carcinoma: A California Cancer Consortium study (CCC-P).

11082 Background: BAY 43-9006 is a multi-targeted tyrosine kinase inhibitor of c and b-Raf, VEGFR 2/3 and PDGFR. Mutations of K-ras oncogene are noted in 80%- 90% of pancreatic adenocarcinoma. The CCC-P performed a randomized phase II study of BAY 43-9006 vs. BAY 43-9006 with gemcitabine in metastatic pancreatic cancer. The primary objective was to determine the response rate (RR), secondary objectives were to determine 6 month overall survival (OS), 3 month progression free survival (PFS) and toxicity.,Chemo-naive patients (pts) were randomized to receive (Arm A) single agent BAY 43-9006 400 mg po BID for 3 weeks on/1 week off or (Arm B) same regimen BAY 43-9006 with gemcitabine 1,000 mg/m2 at 10 mg/m/minute weekly for 3 weeks/1 week off. Pts progressing on single agent BAY 43-9006 (Arm A) were crossed-over to Arm B. Response was assessed every 8 weeks.,52 pts were accrued. Of the 15 pts in Arm A, 7 pts crossed over to Arm B. The median number of cycles was 2.3 for Arm A and 2.9 for Arm B. One pt responded in Arm B. Median PFS and 3-month (mo) PFS were: 2.3 mos (1.2 to 5.7) and 0.36±0.13 in Arm A, and 2.9 mos (2.1 to 4.3) and 55 ± 0.08 in Arm B. Median OS and 6-mo OS were: 4.3 mos and 0.47 ± 0.13 in Arm A, and 6.5 mos and 0.55 ± 0.08 in Arm B. There were more grade 3+ toxicities in Arm B vs. Arm A including hematologic toxicity (11/ 2), liver function abnormalities (3/16) and fatigue (7/1).,The addition of BAY43-90006 to gemcitabine did not demonstrate significant activity in pts with metastatic pancreatic cancer. Supported by NO1 CM-62209. [Table: see text] No significant financial relationships to disclose.