522 POSTER Immunoglobulin G fragment C receptor polymorphisms and clinical outcome of EGFR-expressing metastatic colorectal cancer patients treated with cetuximab-based therapy

Negri, F.; Musolino, Antonino; Naldi, Nadia; Bortesi, Beatrice; Boni, C.; Bisagni, Giancarlo; Camisa, Roberta; Ardizzoni, Andrea

doi:10.1016/s1359-6349(07)70461-5

Cited by 3 publications

(2 citation statements)

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“…Polymorphisms in fragment c gamma receptors, surface receptors for immunoglobulin G located on immune effector cells (such as natural killer lymphocytes and macrophages), are also of interest as potential markers of response to EGFR-targeted monoclonal antibodies, although data are conflicting at present ( 109 , 114 – 116 ). Fragment c gamma receptors are thought to play a role in antibody-dependent cell-mediated cytotoxicity, which has been postulated as an additional mechanism of action for the IgG1 type of monoclonal antibodies, such as cetuximab, rituximab, and trastuzumab ( 117 ).…”

Section: Predicting Response: Molecular Biomarkersmentioning

confidence: 99%

Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor–Targeted Therapy in Metastatic Colorectal Cancer

Siena

Sartore-Bianchi

Nicolantonio

et al. 2009

JNCI: Journal of the National Cancer Institute

481

365

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The monoclonal antibodies panitumumab and cetuximab that target the epidermal growth factor receptor (EGFR) have expanded the range of treatment options for metastatic colorectal cancer. Initial evaluation of these agents as monotherapy in patients with EGFR-expressing chemotherapy-refractory tumors yielded response rates of approximately 10%. The realization that detection of positive EGFR expression by immunostaining does not reliably predict clinical outcome of EGFR-targeted treatment has led to an intense search for alternative predictive biomarkers. Oncogenic activation of signaling pathways downstream of the EGFR, such as mutation of KRAS, BRAF, or PIK3CA oncogenes, or inactivation of the PTEN tumor suppressor gene is central to the progression of colorectal cancer. Tumor KRAS mutations, which may be present in 35%–45% of patients with colorectal cancer, have emerged as an important predictive marker of resistance to panitumumab or cetuximab treatment. In addition, among colorectal tumors carrying wild-type KRAS, mutation of BRAF or PIK3CA or loss of PTEN expression may be associated with resistance to EGFR-targeted monoclonal antibody treatment, although these additional biomarkers require further validation before incorporation into clinical practice. Additional knowledge of the molecular basis for sensitivity or resistance to EGFR-targeted monoclonal antibodies will allow the development of new treatment algorithms to identify patients who are most likely to respond to treatment and could also provide rationale for combining therapies to overcome primary resistance. The use of KRAS mutations as a selection biomarker for anti-EGFR monoclonal antibody (eg, panitumumab or cetuximab) treatment is the first major step toward individualized treatment for patients with metastatic colorectal cancer.

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Section: Predicting Response: Molecular Biomarkersmentioning

confidence: 99%

Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor–Targeted Therapy in Metastatic Colorectal Cancer

Siena

Sartore-Bianchi

Nicolantonio

et al. 2009

JNCI: Journal of the National Cancer Institute

481

365

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“…Preclinical data also suggest that cetuximab may induce antibodydependent cellular cytotoxicity (ADCC) [13][14][15]. However, a recent report failed to demonstrate cetuximab-induced ADCC and this phenomenon has not yet been shown to be clinically relevant [16].…”

Section: Anti-epidermal Growth Factor Receptor Therapy In the Treatmementioning

confidence: 99%

Anti–Epidermal Growth Factor Receptor Monotherapy in the Treatment of Metastatic Colorectal Cancer: Where Are We Today?

2009

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Over the past 10 years there has been a significant increase in the armamentarium of agents available for use in the treatment of advanced colorectal cancer (CRC). Among these new agents are two monoclonal antibodies targeting the epidermal growth factor receptor (EGFR): cetuximab, a mousehuman chimeric monoclonal antibody, and panitumumab, a fully human monoclonal antibody. Both are approved as monotherapy for the treatment of chemotherapy-refractory advanced CRC. Cetuximab is also indicated for use in combination with irinotecan. Here, we review 10 reports of phase II and III clinical studies of patients treated with panitumumab or cetuximab monotherapy. The clinical trials demonstrate similar efficacy profiles for advanced CRC patients treated with panitumumab and cetuximab monotherapy, with some differences in their adverse event profiles. In addition, the recent results of retrospective tumor KRAS gene mutational analyses in CRC patients treated with anti-EGFR monotherapy are reviewed. Data from the clinical trials reviewed here clearly demonstrate that anti-EGFR monotherapy is an effective treatment modality for patients with chemotherapy-refractory advanced CRC. The Oncologist

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Molecular Predictors of Response to Chemotherapy in Colorectal Cancer

Dienstmann¹,

Vilar²,

Tabernero³

2011

The Cancer Journal

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Colorectal cancer (CRC) is one of the leading causes of cancer mortality worldwide. In the last decade, median overall survival has increased significantly with the introduction of new cytotoxics and biologic therapies. Notably, the definition of molecular markers predicting benefit with epidermal growth factor receptor (EGFR)-targeted agents has led to important advances in the personalized treatment of CRC. Data derived from multiple phase III trials have indicated that KRAS mutations can be considered a highly specific negative biomarker of response to anti-EGFR monoclonal antibodies. The predictive value of additional mutations and deregulations of the signaling pathways downstream of the EGFR such as BRAF, NRAS, PIK3CA, or PTEN is under intensive investigation. In addition, status of microsatellite instability and molecular markers related to the metabolism of chemotherapy agents has shown promising ability to select patients with higher chances of response to cytotoxic agents. Although attempts to identify predictive factors for efficacy to antiangiogenic therapies have been disappointing, further research on this field will maximize their therapeutic index. Determination of molecular predictive factors before selection of chemotherapy is rapidly approaching us to the paradigm of individualized treatment of CRC.

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522 POSTER Immunoglobulin G fragment C receptor polymorphisms and clinical outcome of EGFR-expressing metastatic colorectal cancer patients treated with cetuximab-based therapy

Cited by 3 publications

References 0 publications

Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor–Targeted Therapy in Metastatic Colorectal Cancer

Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor–Targeted Therapy in Metastatic Colorectal Cancer

Anti–Epidermal Growth Factor Receptor Monotherapy in the Treatment of Metastatic Colorectal Cancer: Where Are We Today?

Molecular Predictors of Response to Chemotherapy in Colorectal Cancer

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