Figitumumab in patients with refractory metastatic colorectal cancer previously treated with standard therapies: a nonrandomized, open-label, phase II trial

• Published in: Cancer chemotherapy and pharmacology Vol. 73; no. 4; pp. 695 - 702
• Main Authors: Becerra, Carlos R., Salazar, Ramon, Garcia-Carbonero, Rocio, Thomas, Anne L., Vázquez-Mazón, Federico J., Cassidy, James, Maughan, Tim, Castillo, Manuel Gallén, Iveson, Tim, Yin, Donghua, Green, Stephanie, Bergsland, Emily K.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-04-2014; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cancer Research; Cohort Studies; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Metastasis; Neoplasm Staging; Oncology; Original Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival Analysis; Tumors; Phase II; Safety; Figitumumab; Metastatic colorectal cancer; Antineoplastic agent; Human; Treatment resistance; Rectal disease; Toxicity; Colorectal cancer; Monoclonal antibody; Malignant tumor; Metastasis; Standards; Colonic disease; Treatment; Phase II trial; Digestive diseases; Intestinal disease; Advanced stage; Cancer
• DOI: 10.1007/s00280-014-2391-2
• EISSN: 1432-0843
• ISSN: 0344-5704

Purpose
Figitumumab (CP-751,871) is a human IgG2 monoclonal antibody that binds and down-regulates insulin-like growth factor receptor-1 (IGF-1R) and inhibits activation of this receptor by IGF-1 and IGF-2. This nonrandomized, open-label, single-arm, phase II trial evaluated the antitumor activity and safety of figitumumab in patients with metastatic colorectal cancer that was refractory to ≥2 systemic therapies.
Methods
Cohorts A and B received intravenous figitumumab 20 and 30 mg/kg in 3-week cycles, respectively. Both received loading doses (20 or 30 mg/kg) on days 1 and 2 of cycle 1. The primary endpoint was 6-month survival (null hypothesis for each cohort, H
0
: p
6 mo surv
 = 0.45). Secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response, safety, and pharmacokinetics.
Results
A total of 168 patients (Cohort A,
n
 = 85; Cohort B,
n
 = 83) received figitumumab. Estimated 6-month survival was 49.4 % (95 % CI 38.8–60.0) in Cohort A and 44.1 % (95 % CI 33.4–54.9) in Cohort B. Median OS was 5.8 and 5.6 months, respectively; median PFS was 1.4 months in both cohorts. No objective partial or complete responses occurred. The respective rates of treatment discontinuation due to treatment-related adverse events (AEs) were 5 and 7 %. The most common grade 3/4 nonhematologic AEs in both cohorts were hyperglycemia and asthenia. No grade 4 hematologic laboratory abnormalities occurred. Most deaths were reported as due to progressive disease; none were due to figitumumab.
Conclusion
Six-month survival data do not support further study of figitumumab 20 or 30 mg/kg in this patient population.