Global, multicenter, randomized, phase ii trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer Journal Article
| Authors: | Wolpin, B. M.; O'Reilly, E. M.; Ko, Y. J.; Blaszkowsky, L. S.; Rarick, M.; Rocha Lima, C. M.; Ritch, P.; Chan, E.; Spratlin, J.; Macarulla, T.; McWhirter, E.; Pezet, D.; Lichinitser, M.; Roman, L.; Hartford, A.; Morrison, K.; Jackson, L.; Vincent, M.; Reyno, L.; Hidalgo, M. |
| Article Title: | 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/m2 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. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. |
| Keywords: | immunohistochemistry; adult; cancer survival; controlled study; human tissue; aged; unclassified drug; major clinical study; clinical trial; drug tolerability; fatigue; neutropenia; ascites; drug efficacy; drug safety; drug withdrawal; monotherapy; gemcitabine; chemotherapy; antigen expression; phase 2 clinical trial; anemia; randomized controlled trial; thrombocytopenia; monoclonal antibody; abdominal pain; asthenia; hyperglycemia; loading drug dose; lung embolism; chemotherapy induced emesis; multicenter study; drug response; scoring system; pancreas adenocarcinoma; hyperbilirubinemia; pancreatic cancer; cancer tissue; prostate stem cell antigen; cholestasis; metastatic disease; ags 1c4d4; metastatic pancreatic adenocarcinoma |
| Journal Title: | Annals of Oncology |
| Volume: | 24 |
| Issue: | 7 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2013-07-01 |
| Start Page: | 1792 |
| End Page: | 1801 |
| Language: | English |
| DOI: | 10.1093/annonc/mdt066 |
| PROVIDER: | scopus |
| PMCID: | PMC3716216 |
| PUBMED: | 23448807 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 October 2013" - "Art. No.: mdt066" - "CODEN: ANONE" - "Source: Scopus" |
