TRAIL receptor agonist conatumumab with modified FOLFOX6 plus bevacizumab for
first-line treatment of metastatic colorectal cancer: A randomized phase 1b/2
trial.
Author(s): Fuchs CS(1), Fakih M, Schwartzberg L, Cohn AL, Yee L, Dreisbach L, Kozloff MF,
Hei YJ, Galimi F, Pan Y, Haddad V, Hsu CP, Sabin A, Saltz L.
Affiliation(s): Author information:
(1)Dana-Farber Cancer Institute, Boston, Massachusetts.
Publication date & source: 2013, Cancer. , 119(24):4290-8
BACKGROUND: In patients with previously untreated metastatic colorectal cancer
(mCRC), we conducted a phase 1b/randomized phase 2 trial to define the safety,
tolerability, and efficacy of mFOLFOX6 plus bevacizumab (mFOLFOX6/bev) with
conatumumab, an investigational, fully human monoclonal IgG1 antibody that
specifically activates death receptor 5 (DR5).
METHODS: Twelve patients were enrolled in a phase 1b open-label dose-escalation
trial of conatumumab with mFOLFOX6/bev; thereafter, 190 patients were randomized
1:1:1 to receive mFOLFOX6/bev in combination with 2 mg/kg conatumumab, 10 mg/kg
conatumumab, or placebo. Therapy cycles were repeated every 2 weeks until disease
progression or the occurrence of unacceptable toxicity.
RESULTS: In phase 1b, conatumumab with mFOLFOX6/bev was tolerated without
apparent added toxicity over mFOLFOX6/bev alone. In phase 2, conatumumab with
mFOLFOX6/bev did not confer a benefit in progression-free survival when compared
with placebo with mFOLFOX6/bev. Toxicity was similar in all treatment arms.
Following treatment, similar increases in circulating caspase-3 levels were
observed in all arms.
CONCLUSIONS: Conatumumab with mFOLFOX6/bev did not offer improved efficacy over
the same chemotherapy with placebo in first-line treatment of patients with mCRC.
These data do not support further development of conatumumab in advanced CRC.
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