Cetuximab and biomarkers in non-small-cell lung carcinoma

Figures & data

Figure 1 The EGFR signaling cascade.

Notes: Schematic representation of the EGFR signaling axis including its most important downstream targets. Molecular categories are as shown in the color scheme. A direct arrow represents direct interaction, dotted arrows represent translocation into different subcellular compartments, and blunted line represents inhibitory effects. The grey broken line represents the interface between cytoplasm and nucleus.
Abbreviation: EGFR, epidermal growth factor receptor.

Figure 2 The mechanism of cetuximab action.

Notes: Schematic representation of how cetuximab mediates its antitumor activity. The antibody binding to epidermal growth factor receptor prevents receptor dimerization, leading to inhibition of receptor function as shown. Cetuximab binding also fosters receptor internalization and promotes antibody-dependent cell cytotoxicity. The resulting outcomes include disruption of apoptosis,^{54,60,102,103} angiogenesis,^{54,60,103,104} proliferation,^103,105,106 invasion,^44,107,108 and metastasis.^{58,102,105,109}
Abbreviation: EGFR, epidermal growth factor receptor.

Table 1 An overview of ongoing clinical trials evaluating biomarker status in cetuximab therapy

Sr no	Trial number	Phase status	Drugs compared	Target patient number	Organization/Institute	Purpose	Target marker	Outcome
Closed
1	NCT00397384	I	Erlotinib and cetuximab	49	Vanderbilt-Ingram Cancer Center	To study the side effects and best dose of erlotinib when given together with cetuximab	K-ras wild-type	In progress
2	NCT00085501	II	Paclitaxel, carboplatin, and cetuximab	180	Southwest Oncology Group	Cetuximab with or after combination therapy	EGFR and downstream targets	In progress
3	NCT00533949	III	Carboplatin/paclitaxel ± cetuximab and high/standard dose radiation therapy	500	Radiation Therapy Oncology Group	Effect of combination of combined regimen in stage III patients not amenable to surgery	EGFR expression	In progress
Open
4	NCT01263782	II	Carboplatin and pemetrexed ± bevacizumab, cetuximab, or cixutumumab	300	MD Anderson Cancer Center	If biomarkers can predict appropriate NSCLC treatment	Not specified, patients required to be EGFR wild-type	Recruiting
5	NCT00946712	III	Carboplatin and paclitaxel ± bevacizumab ± cetuximab	1546	Southwest Oncology Group	Evaluation of carboplatin and paclitaxel with or without bevacizumab and/or cetuximab therapy	EGFR IHC, EGFR, FISH, and K-ras mutation	Recruiting
6	NCT00979212	II	Chemoradiotherapy with or without cetuximab/panitumumab	97	Radiation Therapy Oncology Group	Effect of radiation with/or without cetuximab/panitumumab (study for cetuximab closed as of 05/14/10)	EGFR, K-ras mutation status, and FDG-PET/CT	Recruiting for panitumumab
7	NCT00408499	I, II	Erlotinib and cetuximab	62	University of California, Davis	To study the side effects and best dose of erlotinib and cetuximab in recurrent stage III or stage IV NSCLC	EGFR expression, K-ras mutation, pMAPK, pAKT, p27, and Ki-67	Recruiting
8	NCT00950365	II	Erlotinib and cetuximab	82	Montefiore Medical Center	To study the side effects and best dose of erlotinib and cetuximab in progressive or recurrent stage III or stage IV NSCLC	Not specified	Recruiting
9	NCT01451632	I	MM-121 (SAR256212) + irinotecan + cetuximab	45	Merrimack Pharmaceuticals and sanofi-aventis	Safety, tolerability, and pharmacokinetics of MM-121, cetuximab and irinotecan	Not specified	Recruiting

Abbreviations: EGFR, epidermal growth factor receptor; NSCLC, non-small-cell lung carcinoma; IHC, immunohistochemistry; FISH, fluorescence-in-situ hybridization; FDG-PET, fluoro-deoxyglucose positron emission tomography (FDG PET); CT, computed tomography; pMAPK, phosphorylated mitogen activated protein kinase; K-ras, Kirsten rat sarcoma viral oncogene homolog.

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