H L Kindler1, D A Richards2, L E Garbo3, E B Garon4, J J Stephenson5, C M Rocha-Lima6, H Safran7, D Chan8, D M Kocs9, F Galimi10, J McGreivy11, S L Bray12, Y Hei10, E G Feigal10, E Loh11, C S Fuchs13. 1. Section of Hematology/Oncology, University of Chicago Medical Center, Chicago. Electronic address: hkindler@medicine.bsd.uchicago.edu. 2. US Oncology Research, Tyler. 3. US Oncology Research, Houston. 4. David Geffen School of Medicine at University of California Los Angeles/Translational Oncology Research International Network, Los Angeles. 5. Department of Experimental Therapeutics, Greenville Hospital System University Medical Center, Greenville. 6. Department of Medicine, University of Miami/Sylvester Comprehensive Cancer Center, Miami. 7. The Brown University Oncology Group, Rhode Island Hospital, Providence. 8. Cancer Care Associates Medical Group, Inc., Redondo Beach. 9. US Oncology Research, Round Rock. 10. Global Development, Amgen Inc., Thousand Oaks. 11. Global Development, Amgen Inc., South San Francisco, USA. 12. Department of Biostatistics and Epidemiology, Amgen Ltd, Cambridge, UK. 13. Department of Medical Oncology/Solid Tumor Oncology, Dana-Farber Cancer Institute, Boston, USA.
Abstract
BACKGROUND: We evaluated the efficacy and safety of ganitumab (a mAb antagonist of insulin-like growth factor 1 receptor) or conatumumab (a mAb agonist of human death receptor 5) combined with gemcitabine in a randomized phase 2 trial in patients with metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with a previously untreated metastatic pancreatic adenocarcinoma and an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 were randomized 1 : 1 : 1 to i.v. gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) combined with open-label ganitumab (12 mg/kg every 2 weeks [Q2W]), double-blind conatumumab (10 mg/kg Q2W), or double-blind placebo Q2W. The primary end point was 6-month survival rate. Results In total, 125 patients were randomized. The 6-month survival rates were 57% (95% CI 41-70) in the ganitumab arm, 59% (42-73) in the conatumumab arm, and 50% (33-64) in the placebo arm. The grade ≥3 adverse events in the ganitumab, conatumumab, and placebo arms, respectively, included neutropenia (18/22/13%), thrombocytopenia (15/17/8%), fatigue (13/12/5%), alanine aminotransferase increase (15/5/8%), and hyperglycemia (18/2/3%). CONCLUSIONS:Ganitumab combined with gemcitabine had tolerable toxicity and showed trends toward an improved 6-month survival rate and overall survival. Additional investigation into this combination is warranted. Conatumumab combined with gemcitabine showed some evidence of activity as assessed by the 6-month survival rate.
RCT Entities:
BACKGROUND: We evaluated the efficacy and safety of ganitumab (a mAb antagonist of insulin-like growth factor 1 receptor) or conatumumab (a mAb agonist of humandeath receptor 5) combined with gemcitabine in a randomized phase 2 trial in patients with metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with a previously untreated metastatic pancreatic adenocarcinoma and an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 were randomized 1 : 1 : 1 to i.v. gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) combined with open-label ganitumab (12 mg/kg every 2 weeks [Q2W]), double-blind conatumumab (10 mg/kg Q2W), or double-blind placebo Q2W. The primary end point was 6-month survival rate. Results In total, 125 patients were randomized. The 6-month survival rates were 57% (95% CI 41-70) in the ganitumab arm, 59% (42-73) in the conatumumab arm, and 50% (33-64) in the placebo arm. The grade ≥3 adverse events in the ganitumab, conatumumab, and placebo arms, respectively, included neutropenia (18/22/13%), thrombocytopenia (15/17/8%), fatigue (13/12/5%), alanine aminotransferase increase (15/5/8%), and hyperglycemia (18/2/3%). CONCLUSIONS:Ganitumab combined with gemcitabine had tolerable toxicity and showed trends toward an improved 6-month survival rate and overall survival. Additional investigation into this combination is warranted. Conatumumab combined with gemcitabine showed some evidence of activity as assessed by the 6-month survival rate.
Authors: Erik L Brincks; Tamara A Kucaba; Britnie R James; Katherine A Murphy; Kathryn L Schwertfeger; Veena Sangwan; Sulagna Banerjee; Ashok K Saluja; Thomas S Griffith Journal: FEBS J Date: 2015-10-18 Impact factor: 5.542
Authors: Chunxia Du; Annacarolina da Silva; Vicente Morales-Oyarvide; Brian M Wolpin; Jonathan A Nowak; Andressa Dias Costa; Margaret M Kozak; Richard F Dunne; Douglas A Rubinson; Kimberly Perez; Yohei Masugi; Tsuyoshi Hamada; Lauren K Brais; Chen Yuan; Ana Babic; Matthew D Ducar; Aaron R Thorner; Andrew Aguirre; Matthew H Kulke; Kimmie Ng; Thomas E Clancy; Jennifer J Findeis-Hosey; Daniel T Chang; Jason L Hornick; Charles S Fuchs; Shuji Ogino; Albert C Koong; Aram F Hezel Journal: Cancer Epidemiol Biomarkers Prev Date: 2020-05-28 Impact factor: 4.254