Randomized, phase II study of the insulin-like growth factor-1 receptor inhibitor IMC-A12, with or without cetuximab, in patients with cetuximab- or panitumumab-refractory metastatic colorectal cancer Journal Article


Authors: Reidy, D. L.; Vakiani, E.; Fakih, M. G.; Saif, M. W.; Hecht, J. R.; Goodman-Davis, N.; Hollywood, E.; Shia, J. R.; Schwartz, J.; Chandrawansa, K.; Dontabhaktuni, A.; Youssoufian, H.; Solit, D. B.; Saltz, L. B.
Article Title: Randomized, phase II study of the insulin-like growth factor-1 receptor inhibitor IMC-A12, with or without cetuximab, in patients with cetuximab- or panitumumab-refractory metastatic colorectal cancer
Abstract: Purpose To evaluate the safety and efficacy of IMC-A12, a human monoclonal antibody (mAb) that blocks insulin-like growth factor receptor-1 (IGF-1R), as monotherapy or in combination with cetuximab in patients with metastatic refractory anti-epidermal growth factor receptor (EGFR) mAb colorectal cancer. Methods A randomized, phase II study was performed in which patients in arm A received IMC-A12 10 mg/kg intravenously (IV) every 2 weeks, while patients in arm B received this same dose of IMC-A12 plus cetuximab 500 mg/m(2) IV every 2 weeks. Subsequently, arm C (same combination treatment as arm B) was added to include patients who had disease control on a prior anti-EGFR mAb and wild-type KRAS tumors. Archived pretreatment tumor tissue was obtained when possible for KRAS, PIK3CA, and BRAF genotyping, and immunohistochemistry was obtained for pAKT as well as IGF-1R. Results Overall, 64 patients were treated (median age, 61 years; range, 40 to 84 years): 23 patients in arm A, 21 in arm B, and 20 in arm C. No antitumor activity was seen in the 23 patients treated with IMC-A12 monotherapy. Of the 21 patients randomly assigned to IMC-A12 plus cetuximab, one patient (with KRAS wild type) achieved a partial response, with disease control lasting 6.5 months. Arm C (all patients with KRAS wild type), however, showed no additional antitumor activity. Serious adverse events thought possibly related to IMC-A12 included a grade 2 infusion-related reaction (2%; one of 64 patients), thrombocytopenia (2%; one of 64 patients), grade 3 hyperglycemia (2%; one of 64 patients), and grade 1 pyrexia (2%, one of 64 patients). Conclusion IMC-A12 alone or in combination with cetuximab was insufficient to warrant additional study in patients with colorectal cancer refractory to EGFR inhibitors.
Keywords: antibody; pathway; head; vivo
Journal Title: Journal of Clinical Oncology
Volume: 28
Issue: 27
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2010-09-20
Start Page: 4240
End Page: 4246
Language: English
ACCESSION: ISI:000281909700022
DOI: 10.1200/jco.2010.30.4154
PROVIDER: wos
PMCID: PMC3296668
PUBMED: 20713879
Notes: --- - Article - "Source: Wos"
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MSK Authors
  1. Leonard B Saltz
    580 Saltz
  2. David Solit
    431 Solit
  3. Diane Lauren Reidy
    146 Reidy
  4. Jinru Shia
    450 Shia
  5. Efsevia Vakiani
    162 Vakiani