O2-13-3 - A Phase I/Ii Trial of Weekly Nab-Paclitaxel(Nab-P)+ Gemcitabine(G) with Metastatic Pancreatic Cancer(Mpc)

Abstract

Background: In the phase III study for MPC, nab-P (ABI-007) + G regimen significantly improved overall survival (OS) compared with G regimen (median OS, 8.5 months (M) vs 6.7 M; Hazard Ratio, 0.72; P < 0.001) [Von Hoff D, et al., 2013]. Nab-P was approved for the treatment of pancreatic cancer by the FDA in September 2013 and the EMA in January 2014. We conducted phase I/ II study of nab-P+ G regimen in Japanese patients (pts) with MPC.Methods: Eligible criteria were; definitive histologically or cytologically confirmed MPC, no prior chemotherapy, one or more measurable metastatic tumors (RECIST ver1.1 criteria), ECOG performance status (PS) 0-1, age <80 and ≥ 20, adequate organ functions. Pts received nab-P 125 mg/m2, followed by G 1000 mg/m2 on days 1, 8, and 15 every 4 weeks. The primary endpoint was to evaluate the overall response rate (ORR) according to RECIST guidelines by the independent review; threshold and expected ORR were 10% and 30%. The calculated sample size was 29 pts at one-side 5% significance level and 80% power.Results: A total of 34 pts were enrolled between November 2012 and July 2013. The median age was 64 years, 13 pts had an ECOG PS of 1, 14 pts had pancreatic head tumors. The ORR was 44.1%. The median progression free survival was 5.6 M. The median follow-up period was 4.7M (range, 2.8-10.5). The median survival time had not been reached. The most common toxicities of grade 3/4 were neutropenia (23 pts, 67.6%), anemia (5 pts, 14.7%), thrombocypenia (2 pts, 5.9%), peripheral neuropathy (2 pts, 5.9%) and diarrhea (2 pts, 5.9%). Febrile neutropenia was observed in 1 pt (2.9%) but there were no treatment-related deaths.Conclusion: Nab-P+ G regimen showed promising efficacy with well-tolerated toxicities. Our result suggested nab-P+ G regimen can be one of the first-line standard treatment in Japanese pts with MPC as well as Western pts. Clinical trial information: JapicCTI-121987.