Abstract |
Overexpression of insulin-like growth factor receptor type 1 (IGF-1R) may promote tumor development and progression in some cancer patients. Our objective was to assess tumor uptake of fluorodeoxyglucose by positron-emission tomography in patients with chemotherapy-refractory colorectal cancer treated with an anti- insulin-like growth factor receptor type 1 (anti-IGF-1R) monoclonal antibody, robatumumab. This was a randomized, open-label study with two periods (P1 and P2). Patients were randomized 3:1 into treatment arms R/R and C/R that received, respectively, one cycle of 0.3 mg/kg robatumumab or one or more cycles of second-line chemotherapy in P1, followed in either case by 10 mg/kg robatumumab biweekly in P2. The primary measure of fluorodeoxyglucose uptake was maximum standardized uptake value (SUV(max)). The primary endpoint was the proportion of patients in the R/R arm having a mean percent decrease from baseline in SUV(max) (DiSUV) greater than 20% 12-14 days postdose in P2. Secondary endpoints included Response Evaluation Criteria in Solid Tumors (RECIST)-defined tumor response and pharmacodynamic measures of target engagement. Among 41 patients who were evaluable for the primary endpoint, seven (17%, 95% CI 7%-32%) had DiSUV greater than 20%. Fifty robatumumab-treated patients were evaluable for RECIST-defined tumor response and six (12%) had stable disease lasting greater than or equal to 7 weeks in P2. Pharmacodynamic endpoints indicated target engagement after dosing with 10 mg/kg robatumumab, but not 0.3 mg/kg. The most frequently reported adverse events were fatigue/ asthenia, nausea, anorexia, and gastrointestinal disturbances. In this study, few patients with chemotherapy-refractory colorectal cancer appeared to benefit from treatment with the IGF-1R antagonist robatumumab.
|
Authors | Edward H Lin, Heinz-Josef Lenz, Mansoor N Saleh, Mary J Mackenzie, James A Knost, Kumudu Pathiraja, Ronald B Langdon, Siu-Long Yao, Brian D Lu |
Journal | Cancer medicine
(Cancer Med)
Vol. 3
Issue 4
Pg. 988-97
(Aug 2014)
ISSN: 2045-7634 [Electronic] United States |
PMID | 24905030
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Copyright | © 2014 Merck & Co., Inc. Cancer Medicine published by John Wiley & Sons Ltd. |
Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Receptor, IGF Type 1
- robatumumab
|
Topics |
- Aged
- Antibodies, Monoclonal
(adverse effects, therapeutic use)
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
(adverse effects, therapeutic use)
- Colorectal Neoplasms
(drug therapy, pathology)
- Fatigue
(chemically induced)
- Female
- Humans
- Male
- Middle Aged
- Receptor, IGF Type 1
(immunology)
- Treatment Outcome
|