The Treatment of Colorectal Carcinoma With Monoclonal Antibodies: In reply

by Dr. med. Sebastian Stintzing, Prof. Dr. med. Volker Heinemann, PD Dr. med. Andreas Jung, Dr. med. Nicolas Moosmann, Prof. Dr. med. Wolfgang Hiddemann, Prof. Dr. med. Thomas Kirchner in volume 12/2009

As Tsamaloukas rightly comments, antibody mediated cellular cytotoxicity may be a further mechanism of action of the anti-EGFR antibody cetuximab. The studies reported by Zhang (1) and Bibeau (2) are the first retrospective studies that have shown a clinical effect of the FcgRIIA(CD64) polymorphism und the FcgRIIIa (CD16a) polymorphism of the Fc-receptor on macrophages and/or natural killer cells on ADCC.

It needs to be emphasized, however, that larger studies (3) have not shown a clear indication of the efficacy of cetuximab on KRAS mutated tumors as described by Bibeau. In these studies, which were also retrospective investigations, the use of cetuximab in KRAS mutated patients with colorectal cancers did not result in a significantly prolonged progression-free survival. In one study, patients who were treated with FOLFOX and cetuximab and had a KRAS mutation responded less well and had a shorter progression-free survival interval (3) than patients treated with FOLFOX. Prospective studies with larger numbers of patients are thus needed to better assess the concrete effect of ADCC.

Because of the currently unclear importance of ADCC, anti-EGFR antibodies should not be used in patients who have KRAS mutations.
DOI: 10.3238/arztebl.2009.0526b


Prof. Dr. med. Volker Heinemann
Dr. med. Sebastian Stintzing
Medizinische Klinik und Poliklinik III
Klinikum der LMU München, Großhadern
Marchioninistr. 15
81377 München, Germany
[e-mail]
[e-mail]

Conflict of interest statement
The authors of both the letter and of the reply declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors.

References

1. Zhang W et al.: FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol 2007; 25: 3712–8.

2. Bibeau F et al.: Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol 2009; 27: 1122–9.

3. Bokemeyer C et al.: Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 2009; 27(5): 663–71.

4. Stintzing S, Heinemann V, Jung A, Moosmann N, Hiddemann W, Kirchner T: The treatment of colorectal carcinoma with monoclonal antibodies—the importance of KRAS mutation analysis and EGFR status [Behandlung des kolorektalen Karzinoms mit monoklonalen Antikörpern – Bedeutung der KRAS Mutationsanalyse und des EGFR-Status]. Dtsch Arztebl Int 2009; 106: 202–6.