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.
| Original language | English |
|---|---|
| Article number | mds142 |
| Pages (from-to) | 2834-2842 |
| Number of pages | 9 |
| Journal | Annals of Oncology |
| Volume | 23 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2012 |
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Keywords
- AMG 479
- Conatumumab
- Ganitumab
- Gemcitabine
- Pancreatic cancer
- Phase 2 trial
ASJC Scopus subject areas
- Oncology
- Hematology
Cite this
A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer. / Kindler, H. L.; Richards, D. A.; Garbo, L. E.; Garon, E. B.; Stephenson, J. J.; Rocha-Lima, C. M.; Safran, H.; Chan, D.; Kocs, D. M.; Galimi, F.; Mcgreivy, J.; Bray, S. L.; Hei, Y.; Feigal, E. G.; Loh, E.; Fuchs, C. S.
In: Annals of Oncology, Vol. 23, No. 11, mds142, 01.11.2012, p. 2834-2842.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer
AU - Kindler, H. L.
AU - Richards, D. A.
AU - Garbo, L. E.
AU - Garon, E. B.
AU - Stephenson, J. J.
AU - Rocha-Lima, C. M.
AU - Safran, H.
AU - Chan, D.
AU - Kocs, D. M.
AU - Galimi, F.
AU - Mcgreivy, J.
AU - Bray, S. L.
AU - Hei, Y.
AU - Feigal, E. G.
AU - Loh, E.
AU - Fuchs, C. S.
PY - 2012/11/1
Y1 - 2012/11/1
N2 - 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.
AB - 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.
KW - AMG 479
KW - Conatumumab
KW - Ganitumab
KW - Gemcitabine
KW - Pancreatic cancer
KW - Phase 2 trial
UR - http://www.scopus.com/inward/record.url?scp=84862531853&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862531853&partnerID=8YFLogxK
U2 - 10.1093/annonc/mds142
DO - 10.1093/annonc/mds142
M3 - Article
C2 - 22700995
AN - SCOPUS:84862531853
VL - 23
SP - 2834
EP - 2842
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 11
M1 - mds142
ER -