Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer

Abstract

Background: We evaluated AGS-1C4D4, a fully human monoclonal antibody to prostate stem cell antigen (PSCA), with gemcitabine in a randomized, phase II study of metastatic pancreatic cancer.

Patients and methods: Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and previously untreated, metastatic pancreatic adenocarcinoma were randomly assigned 1:2 to gemcitabine (1000 mg/m(2) weekly seven times, 1 week rest, weekly three times q4weeks) or gemcitabine plus AGS-1C4D4 (48 mg/kg loading dose, then 24 mg/kg q3weeks IV). The primary end point was 6-month survival rate (SR). Archived tumor samples were collected for pre-planned analyses by PSCA expression.

Results: Between April 2009 and May 2010, 196 patients were randomly assigned to gemcitabine (n = 63) or gemcitabine plus AGS-1C4D4 (n = 133). The 6-month SR was 44.4% (95% CI, 31.9-57.5) in the gemcitabine arm and 60.9% (95% CI, 52.1-69.2) in the gemcitabine plus AGS-1C4D4 arm (P = 0.03), while the median survival was 5.5 versus 7.6 months and the response rate was 13.1% versus 21.6% in the two arms, respectively. The 6-month SR was 57.1% in the gemcitabine arm versus 79.5% in the gemcitabine plus AGS-1C4D4 arm among the PSCA-positive subgroup and 31.6% versus 46.2% among the PSCA-negative subgroup.

Conclusions: This randomized, phase II study achieved its primary end point, demonstrating an improved 6-month SR with addition of AGS-1C4D4 to gemcitabine among patients with previously untreated, metastatic pancreatic adenocarcinoma. ClinicalTrials.gov identifier: NCT00902291.

Keywords: chemotherapy; clinical trial; gemcitabine; metastatic disease; pancreatic cancer; prostate stem cell antigen.

Figures

Figure 1.

Duration of (A) overall survival (OS) and (B) progression-free survival (PFS) by treatment arm. (A) OS. (B) PFS.

Figure 2.

Overall survival (OS) of patients receiving (A) gemcitabine and (B) gemcitabine versus gemcitabine plus AGS-1C4D4 by tumor PSCA staining. (A) Gemcitabine arm only. (B) Gemcitabine arm and gemcitabine plus AGS-1C4D4 arm.