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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