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Dear Sir,

We appreciate the critical remarks to our manuscript “Prognostic value of cetuximab related skin toxicity in metastatic colorectal cancer (mCRC) patients and its correlation with parameters of the EGFR signal transduction pathway: Results from a randomized trial of the GERMAN AIO CRC Study Group”.1

As previously stated in our publication, patients treated with panitumumab in the PRIME study developing acneiform skin rash Grade ≥2 had longer progression-free survival (PFS) and overall survival (OS) compared to those with rash Grade 0–1. This observation was made in patients with KRAS wild-type and comparably also with KRAS-mutated tumors.2 Although, in fact, the numbers in our manuscript were quoted incorrectly, the underlying statement remains identical (Table 1).

Table 1. Correlation of worst skin toxicity and outcome in patients with KRAS wild-type compared to KRAS-mutant tumors in FOLFOX plus panitumumab treated patients (PRIME study)2
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As tumors bearing a KRAS mutation do not benefit from panitumumab, and in combination with FOLFOX even show a trend toward shorter survival, the longer survival in patients with KRAS mutant tumors developing acneiform rash during therapy with anti-EGFR antibodies has to be explained by other, until now unknown, factors. Furthermore, it is of interest that patients bearing KRAS wild-type tumors, but developed only skin toxicity Grade 0–1, appeared to have worse outcomes compared to patients with KRAS mutant tumors that got acneiform rash Grade 2–4. Although clear explanations are missing, these data again underline the assumption, that acneiform skin rash, as stated in the title of our manuscript, rather is of prognostic than of predictive value.

We support the opinion that patients with KRAS-mutated tumors, at present time, should not receive anti-EGFR directed agents, regardless if skin toxicity induced by these agents may unveil a subgroup with a more favorable prognosis. We also agree with the statement that the benefit from anti-EGFR agents in patients with codon 13 mutated mCRC still awaits prospective verification. Specifically, we feel that in addition to the different anti-EGFR agents (cetuximab vs. panitumumab) also the chemotherapy backbone (irinotecan vs. oxaliplatin) and possibly also the line of palliative treatment (first-line vs. further line) needs to be taken into account.

Yours sincerely,

References

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  • 1
    Stintzing S, Kapaun C, Laubender RP, et al. Prognostic value of cetuximab related skin toxicity in metastatic colorectal cancer (mCRC) patients and its correlation with parameters of the EGFR signal transduction pathway. Results from a randomized trial of the GERMAN AIO CRC Study Group. Int J Cancer; 2012 doi: 10.1002/ijc.27654. [Epub ahead of print].
  • 2
    Douillard JY, Cassidy J, Jassem J, et al. Randomized, open-label, phase 3 study of panitumumab with FOLFOX4 vs FOLFOX4 alone as 1st-line treatment (tx) for Metastatic Colorectal Cancer (mCRC): efficacy by skin toxicity. J Clin Oncol 2010; 28: 15s (suppl;abstr 3528∧).

Sebastian Stintzing*, Volker Heinemann*, * Department of Oncology and Comprehensive Cancer Center, Klinikum Grosshadern, University of Munich, Germany.