A phase II, multicenter study of cetuximab monotherapy in patients with refractory, metastatic colorectal carcinoma with absent epidermal growth factor receptor immunostaining

Rafal Wierzbicki, Derek J. Jonker, Malcolm J. Moore, Scott R. Berry, Patrick Loehrer, Hagop Youssoufian, Eric K. Rowinsky

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Summary: Purpose To determine antitumor activity of cetuximab monotherapy in patients with refractory metastatic colorectal carcinoma (mCRC) with lack of specific membrane immunostaining for the epidermal growth factor receptor (EGFR). Patients and methods Patients had immunohistochemical (IHC)-determined mCRC with absent EGFR immunostaining that progressed after receiving at least one standard, fluoropyrimidine-containing chemotherapeutic regimen. Absent EGFR immunostaining was defined as the IHC absence of specific membrane staining in ≥500 cancer cells examined in well-preserved tissue. The study was performed prior to results of studies linking cetuximab sensitivity to K-ras mutation status. Patients received 400 mg/m2 of intravenous (i.v.) cetuximab followed by once-weekly i.v. cetuximab 250 mg/m2 until disease progression or unacceptable toxicity. Patients were evaluated for objective response at least every 6 weeks. Kaplan-Meier estimates were calculated for duration of response, time to progression (TTP), and overall survival (OS). Results Seven (8.2%) of 85 mCRC patients whose tumors lacked EGFR immunostaining had major responses following cetuximab treatment. The median duration of response was 5.1 months. Median TTP and OS were 2.5 months and 10.0 months, respectively; the 1-year survival rate was 39.6%. The most frequently reported cetuximab-related adverse events were acneiform dermatitis, fatigue, headache, and dry skin. Conclusion Cetuximab monotherapy produces objective antitumor activity in patients with mCRC that does not express EGFR as determined by IHC. The activity and safety profiles of cetuximab monotherapy in mCRC lacking EGFR immunostaining are similar to previous observations in EGFR IHC-positive disease that was not selected based on K-ras mutation status.

Original languageEnglish
Pages (from-to)167-174
Number of pages8
JournalInvestigational New Drugs
Volume29
Issue number1
DOIs
StatePublished - Feb 2011

Fingerprint

Epidermal Growth Factor Receptor
Multicenter Studies
Colorectal Neoplasms
Mutation
Membranes
Survival
Cetuximab
Kaplan-Meier Estimate
Dermatitis
Reaction Time
Fatigue
Headache
Disease Progression
Neoplasms
Survival Rate
Staining and Labeling
Safety
Skin

Keywords

  • Cetuximab
  • Epidermal growth factor receptor (EGFR)
  • Immunohistochemistry (IHC)
  • Immunostaining
  • Metastatic colorectal cancer (mCRC)

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

A phase II, multicenter study of cetuximab monotherapy in patients with refractory, metastatic colorectal carcinoma with absent epidermal growth factor receptor immunostaining. / Wierzbicki, Rafal; Jonker, Derek J.; Moore, Malcolm J.; Berry, Scott R.; Loehrer, Patrick; Youssoufian, Hagop; Rowinsky, Eric K.

In: Investigational New Drugs, Vol. 29, No. 1, 02.2011, p. 167-174.

Research output: Contribution to journalArticle

Wierzbicki, Rafal ; Jonker, Derek J. ; Moore, Malcolm J. ; Berry, Scott R. ; Loehrer, Patrick ; Youssoufian, Hagop ; Rowinsky, Eric K. / A phase II, multicenter study of cetuximab monotherapy in patients with refractory, metastatic colorectal carcinoma with absent epidermal growth factor receptor immunostaining. In: Investigational New Drugs. 2011 ; Vol. 29, No. 1. pp. 167-174.
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abstract = "Summary: Purpose To determine antitumor activity of cetuximab monotherapy in patients with refractory metastatic colorectal carcinoma (mCRC) with lack of specific membrane immunostaining for the epidermal growth factor receptor (EGFR). Patients and methods Patients had immunohistochemical (IHC)-determined mCRC with absent EGFR immunostaining that progressed after receiving at least one standard, fluoropyrimidine-containing chemotherapeutic regimen. Absent EGFR immunostaining was defined as the IHC absence of specific membrane staining in ≥500 cancer cells examined in well-preserved tissue. The study was performed prior to results of studies linking cetuximab sensitivity to K-ras mutation status. Patients received 400 mg/m2 of intravenous (i.v.) cetuximab followed by once-weekly i.v. cetuximab 250 mg/m2 until disease progression or unacceptable toxicity. Patients were evaluated for objective response at least every 6 weeks. Kaplan-Meier estimates were calculated for duration of response, time to progression (TTP), and overall survival (OS). Results Seven (8.2{\%}) of 85 mCRC patients whose tumors lacked EGFR immunostaining had major responses following cetuximab treatment. The median duration of response was 5.1 months. Median TTP and OS were 2.5 months and 10.0 months, respectively; the 1-year survival rate was 39.6{\%}. The most frequently reported cetuximab-related adverse events were acneiform dermatitis, fatigue, headache, and dry skin. Conclusion Cetuximab monotherapy produces objective antitumor activity in patients with mCRC that does not express EGFR as determined by IHC. The activity and safety profiles of cetuximab monotherapy in mCRC lacking EGFR immunostaining are similar to previous observations in EGFR IHC-positive disease that was not selected based on K-ras mutation status.",
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T1 - A phase II, multicenter study of cetuximab monotherapy in patients with refractory, metastatic colorectal carcinoma with absent epidermal growth factor receptor immunostaining

AU - Wierzbicki, Rafal

AU - Jonker, Derek J.

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AU - Berry, Scott R.

AU - Loehrer, Patrick

AU - Youssoufian, Hagop

AU - Rowinsky, Eric K.

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N2 - Summary: Purpose To determine antitumor activity of cetuximab monotherapy in patients with refractory metastatic colorectal carcinoma (mCRC) with lack of specific membrane immunostaining for the epidermal growth factor receptor (EGFR). Patients and methods Patients had immunohistochemical (IHC)-determined mCRC with absent EGFR immunostaining that progressed after receiving at least one standard, fluoropyrimidine-containing chemotherapeutic regimen. Absent EGFR immunostaining was defined as the IHC absence of specific membrane staining in ≥500 cancer cells examined in well-preserved tissue. The study was performed prior to results of studies linking cetuximab sensitivity to K-ras mutation status. Patients received 400 mg/m2 of intravenous (i.v.) cetuximab followed by once-weekly i.v. cetuximab 250 mg/m2 until disease progression or unacceptable toxicity. Patients were evaluated for objective response at least every 6 weeks. Kaplan-Meier estimates were calculated for duration of response, time to progression (TTP), and overall survival (OS). Results Seven (8.2%) of 85 mCRC patients whose tumors lacked EGFR immunostaining had major responses following cetuximab treatment. The median duration of response was 5.1 months. Median TTP and OS were 2.5 months and 10.0 months, respectively; the 1-year survival rate was 39.6%. The most frequently reported cetuximab-related adverse events were acneiform dermatitis, fatigue, headache, and dry skin. Conclusion Cetuximab monotherapy produces objective antitumor activity in patients with mCRC that does not express EGFR as determined by IHC. The activity and safety profiles of cetuximab monotherapy in mCRC lacking EGFR immunostaining are similar to previous observations in EGFR IHC-positive disease that was not selected based on K-ras mutation status.

AB - Summary: Purpose To determine antitumor activity of cetuximab monotherapy in patients with refractory metastatic colorectal carcinoma (mCRC) with lack of specific membrane immunostaining for the epidermal growth factor receptor (EGFR). Patients and methods Patients had immunohistochemical (IHC)-determined mCRC with absent EGFR immunostaining that progressed after receiving at least one standard, fluoropyrimidine-containing chemotherapeutic regimen. Absent EGFR immunostaining was defined as the IHC absence of specific membrane staining in ≥500 cancer cells examined in well-preserved tissue. The study was performed prior to results of studies linking cetuximab sensitivity to K-ras mutation status. Patients received 400 mg/m2 of intravenous (i.v.) cetuximab followed by once-weekly i.v. cetuximab 250 mg/m2 until disease progression or unacceptable toxicity. Patients were evaluated for objective response at least every 6 weeks. Kaplan-Meier estimates were calculated for duration of response, time to progression (TTP), and overall survival (OS). Results Seven (8.2%) of 85 mCRC patients whose tumors lacked EGFR immunostaining had major responses following cetuximab treatment. The median duration of response was 5.1 months. Median TTP and OS were 2.5 months and 10.0 months, respectively; the 1-year survival rate was 39.6%. The most frequently reported cetuximab-related adverse events were acneiform dermatitis, fatigue, headache, and dry skin. Conclusion Cetuximab monotherapy produces objective antitumor activity in patients with mCRC that does not express EGFR as determined by IHC. The activity and safety profiles of cetuximab monotherapy in mCRC lacking EGFR immunostaining are similar to previous observations in EGFR IHC-positive disease that was not selected based on K-ras mutation status.

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KW - Metastatic colorectal cancer (mCRC)

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