TY - JOUR
T1 - A randomised, phase II study of intetumumab, an anti-α v-integrin mAb, alone and with dacarbazine in stage IV melanoma
AU - Lorigan, Paul
AU - O'Day, S.
AU - Pavlick, A.
AU - Loquai, C.
AU - Lawson, D.
AU - Gutzmer, R.
AU - Richards, J.
AU - Schadendorf, D.
AU - Thompson, J. A.
AU - Gonzalez, R.
AU - Trefzer, U.
AU - Mohr, P.
AU - Chao, D.
AU - Zhong, B.
AU - De Boer, C. J.
AU - Uhlar, C.
AU - Marshall, D.
AU - Gore, M. E.
AU - Lang, Z.
AU - Hait, W.
AU - Ho, P.
PY - 2011/7/26
Y1 - 2011/7/26
N2 - Background: αv integrins are involved in angiogenesis and melanoma tumourigenesis. Intetumumab (CNTO 95) is a fully human anti-αv-integrin monoclonal antibody.Methods:In a multicentre, randomised, phase II study, stage IV melanoma patients were randomised 1: 1: 1: 1 to 1000 mg m2 dacarbazineplacebo (n32), 1000 mg m2 dacarbazine10 mg kg1 intetumumab (n32), 10 mg kg1 intetumumab (n33), or 5 mg kg1 intetumumab (n32) q3w. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), adverse events, and pharmacokinetics.Results:No statistically significant differences in efficacy were observed between groups. In the dacarbazineplacebo, dacarbazineintetumumab, 10 mg kg1 intetumumab, and 5 mg kg1 intetumumab groups, median PFS was 1.8, 2.5, 1.4, and 1.4 months; median OS was 8, 11, 15, and 9.8 months; and ORR of completepartial response was 10, 3, 6, and 0%. Nonlinear intetumumab pharmacokinetics and potential intetumumab-dacarbazine interactions were observed. Transient, asymptomatic, nonrecurring, grade 1-2, uveitic reactions that resolved spontaneously or with topical steroids were seen in 22-30% of intetumumab-treated patients. Low-grade infusion-reaction symptoms (headache, fatigue, nausea, vomiting, fever, chills) were observed, as expected, in 16-73% of dacarbazine-treated patients. No intetumumab-related myelosuppression, laboratory/electrocardiogram abnormalities, or deaths occurred. Conclusion: With its favourable safety profile and a nonsignificant trend towards improved OS, intetumumab merits further investigation in advanced melanoma. © 2011 Cancer Research UK All rights reserved.
AB - Background: αv integrins are involved in angiogenesis and melanoma tumourigenesis. Intetumumab (CNTO 95) is a fully human anti-αv-integrin monoclonal antibody.Methods:In a multicentre, randomised, phase II study, stage IV melanoma patients were randomised 1: 1: 1: 1 to 1000 mg m2 dacarbazineplacebo (n32), 1000 mg m2 dacarbazine10 mg kg1 intetumumab (n32), 10 mg kg1 intetumumab (n33), or 5 mg kg1 intetumumab (n32) q3w. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), adverse events, and pharmacokinetics.Results:No statistically significant differences in efficacy were observed between groups. In the dacarbazineplacebo, dacarbazineintetumumab, 10 mg kg1 intetumumab, and 5 mg kg1 intetumumab groups, median PFS was 1.8, 2.5, 1.4, and 1.4 months; median OS was 8, 11, 15, and 9.8 months; and ORR of completepartial response was 10, 3, 6, and 0%. Nonlinear intetumumab pharmacokinetics and potential intetumumab-dacarbazine interactions were observed. Transient, asymptomatic, nonrecurring, grade 1-2, uveitic reactions that resolved spontaneously or with topical steroids were seen in 22-30% of intetumumab-treated patients. Low-grade infusion-reaction symptoms (headache, fatigue, nausea, vomiting, fever, chills) were observed, as expected, in 16-73% of dacarbazine-treated patients. No intetumumab-related myelosuppression, laboratory/electrocardiogram abnormalities, or deaths occurred. Conclusion: With its favourable safety profile and a nonsignificant trend towards improved OS, intetumumab merits further investigation in advanced melanoma. © 2011 Cancer Research UK All rights reserved.
U2 - 10.1038/bjc.2011.183
DO - 10.1038/bjc.2011.183
M3 - Article
SN - 0007-0920
VL - 105
SP - 346
EP - 352
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 3
ER -
