Multicenter Phase II and Translational Study of Cetuximab in Metastatic Colorectal Carcinoma Refractory to Irinotecan, Oxaliplatin, and Fluoropyrimidines

Lenz, Heinz Josef; Cutsem, Éric Van; Khambata‐Ford, Shirin; Mayer, Robert J.; Gold, Philip J.; Stella, Philip J.; Mirtsching, B.; Cohn, Allen Lee; Pippas, Andrew W.; Azarnia, Nozar; Tsuchihashi, Zenta; Mauro, David; Rowinsky, Eric K.

doi:10.1200/jco.2006.06.7595

Cited by 480 publications

(283 citation statements)

References 47 publications

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“…In BOND I, patients treated with CxIri and developing severe skin rash, RR was 55%, TTP was 8.2 months and median OS was 13.7 months, respectively, and the degree of rash as a predictive marker for RR and OS has been confirmed in many studies (Lenz et al, 2006;Pfeiffer et al, 2007b).…”

Section: Predicting Efficacy Of CX and Pamentioning

confidence: 83%

“…Comparison of Cx and Pa RR for Cx and Pa single agents (8-11%) are very similar in pretreated patients Malik et al, 2005;Lenz et al, 2006;Peeters et al, 2006). There was no improvement in median OS, neither in the Peeters study nor in the BOND I study, but this lack of difference may be caused by the fact that many patients in both studies received salvage therapy upon PD.…”

Section: Role Of Antibody Therapy P Pfeiffer Et Almentioning

confidence: 96%

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Current role of antibody therapy in patients with metastatic colorectal cancer

2007

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Section: Predicting Efficacy Of CX and Pamentioning

confidence: 83%

Section: Role Of Antibody Therapy P Pfeiffer Et Almentioning

confidence: 96%

Current role of antibody therapy in patients with metastatic colorectal cancer

2007

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“…In fact, amplification was found in three patients only. Furthermore, Lenz et al (2006) reported that EGFR amplification is not related to response to cetuximab, questioning the role of EGFR amplification in the prediction of clinical activity of EGFR inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…Cetuximab, a monoclonal antibody, has been demonstrated to produce a 10% response rate in monotherapy and a 20% when combined with irinotecan even in patients refractory to this drug (Cunningham et al, 2004;Lenz et al, 2006). …”

mentioning

confidence: 99%

A combination of gefitinib and FOLFOX-4 as first-line treatment in advanced colorectal cancer patients. A GISCAD multicentre phase II study including a biological analysis of EGFR overexpression, amplification and NF-kB activation

Cascinu

Berardi

Salvagni³

et al. 2007

Br J Cancer

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Interesting activity has been reported by combining chemotherapy with cetuximab. An alternative approach for blocking EGFR function has been the development of small-molecule inhibitors of tyrosine kinase domain such as gefitinib. We designed a multicentre phase II study in advanced colorectal cancer combining gefitinib þ FOLFOX in order to determine the activity and to relate EGFR expression and gene amplification and NF-kB activation to therapeutic results. Patients received FOLFOX-4 regimen plus gefitinib as first-line treatment. Tumour samples were analysed for EGFR protein expression by immunohistochemical analysis and for EGFR gene amplification by fluorescence in situ hybridisation (FISH), chromogenic in situ hybridisation (CISH) and NF-kB activation. Forty-three patients were enrolled into this study; 15 patients experienced a partial response (response rate ¼ 34.9%), whereas other 12 (27.9%) had a stable disease. Median progression-free survival (PFS) was 7.8 months and median overall survival (OS) was 13.9 months. We did not find any relationship with EGFR overexpression, gene amplification, while NF-kB activation was associated with a resistance to therapy. Gefitinib does not seem to increase the activity of FOLFOX in advanced colorectal cancer even in patients overexpressing EGFR or with EGFR amplification. Furthermore, while NF-kB activation seems to predict resistance to chemotherapy as demonstrated 'in vitro' models, gefitinib does not overcome this mechanism of resistance, as reported for cetuximab.

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“…While studies have shown an added benefit for patients receiving cetuximabþirinotecan-based therapy compared to patients receiving cetuximab monotherapy, irinotecan-intolerant patients are likely to receive cetuximab alone. 6,9,19,20 Therefore, we also modeled a cetuximab-only strategy in which patients received 400 mg/m 2 of cetuximab during the first week of therapy and 250 mg/m 2 every week thereafter. Finally, we included a panitumumab-only strategy in which patients received 6 mg/kg of panitumumab every 2 weeks.…”

Section: Chemotherapy Regimensmentioning

confidence: 99%

Cost‐effectiveness of KRAS testing in metastatic colorectal cancer patients in the United States and Germany

Vijayaraghavan

Efrusy²,

Göke

et al. 2012

Intl Journal of Cancer

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The objective of this study was to determine the cost-effectiveness of testing for KRAS mutations before administering EGFR inhibitors such as cetuximab and panitumumab for patients with advanced metastatic colorectal cancer (mCRC) in the United States and Germany. We developed a lifetime Markov model of costs and survival associated with treating mCRC patients to assess the impact of KRAS testing before administering EGFR inhibitor-containing chemotherapy regimens. Overall, combination therapies involving cetuximab plus irinotecan/FOLFIRI had a better life expectancy (25.83 weeks) than cetuximab or panitumumab alone. Use of KRAS testing (assuming KRAS mutant patients receive only irinotecan) was equally effective and saved $12,428 per patient in the United States. When KRAS mutant patients received best supportive care, the life expectancy decreased slightly (24.26 weeks vs. 25.83 weeks) and the costs decreased by $13,501 in the United States and €9,560 in Germany. For patients treated with cetuximab alone, use of KRAS testing to identify mutations lowered costs by $8,040 per patient in the U.S. analysis and €3,856 per patient in the German analysis. For patients treated with panitumumab alone, use of KRAS testing to identify mutations lowered costs by $7,546 per patient in the U.S. analysis and €4,612 per patient in the German analysis. Model results were sensitive to the cost of chemotherapy regimens and the prevalence of KRAS mutations in the population. Under most scenarios, using KRAS testing to select patients for EGFR inhibitor therapy saved $7,500-$12,400 per patient in the United States and €3,900-€9,600 per patient in Germany with equivalent clinical outcomes.

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Multicenter Phase II and Translational Study of Cetuximab in Metastatic Colorectal Carcinoma Refractory to Irinotecan, Oxaliplatin, and Fluoropyrimidines

Cited by 480 publications

References 47 publications

Current role of antibody therapy in patients with metastatic colorectal cancer

Current role of antibody therapy in patients with metastatic colorectal cancer

A combination of gefitinib and FOLFOX-4 as first-line treatment in advanced colorectal cancer patients. A GISCAD multicentre phase II study including a biological analysis of EGFR overexpression, amplification and NF-kB activation

Cost‐effectiveness of KRAS testing in metastatic colorectal cancer patients in the United States and Germany

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