Figitumumab in patients with refractory metastatic colorectal cancer previously treated with standard therapies: a nonrandomized, open-label, phase II trial.
OBJECTIVE
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, H0: p6 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.


CONCLUSIONS
Six-month survival data do not support further study of figitumumab 20 or 30 mg/kg in this patient population.
Texas Oncology-Sammons Cancer Center at Baylor, 3410 Worth Street, Dallas, TX, 75246, USA, Carlos.Becerra@usoncology.com.
Carlos R
CR
Becerra
Ramon
R
Salazar
Rocio
R
Garcia-Carbonero
Anne L
AL
Thomas
Federico J
FJ
Vázquez-Mazón
James
J
Cassidy
Tim
T
Maughan
Manuel Gallén
MG
Castillo
Tim
T
Iveson
Donghua
D
Yin
Stephanie
S
Green
Emily K
EK
Bergsland
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C525021:figitumumab