Methodological Issues of Clinical Research with EGFR Inhibitors

Morabito, Alessandro; Piccirillo, Maria Carmela; Monaco, Katia; Falasconi, Fabiano; Normanno, Nicola; Perrone, Francesco

doi:10.2174/157339407782497031

Cited by 3 publications

(1 citation statement)

References 82 publications

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“…Negative results were similarly observed with the combination of another tyrosine kinase inhibitor, erlotinib, with chemotherapy (TALENT and TRIBUTE studies) [ 26 , 27 ]. Several explanations regarding the lack of an additive effect between tyrosine kinase inhibitors and chemotherapy have been proposed: a mechanistic interaction between gefitinib or erlotinib and chemotherapy, for which the antiproliferative effects of anti-EGFR agents may render tumor cells less sensitive to cytotoxic agents, as suggested by preclinical studies; the possibility that patients who benefit from EGFR-targeted treatments are the same who likely respond to chemotherapy: in this case, the effect of tyrosine kinase inhibitors can be masked by the effect of chemotherapy; finally, the lack of patient selection based on the expression of EGFR [ 28 ].…”

Section: Development Of Gefitinib In “Unselected” Patientsmentioning

confidence: 99%

Gefitinib in Non Small Cell Lung Cancer

Costanzo¹,

Piccirillo²,

Sandomenico³

et al. 2011

BioMed Research International

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Gefitinib is an oral, reversible, tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) that plays a key role in the biology of non small cell lung cancer (NSCLC). Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. Rash, diarrhea, and nausea were the most common adverse events. The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced NSCLC. The subsequent discovery that the presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors prompted phase 2 and 3 trials with gefitinib in the first line-treatment of EGFR-mutated NSCLC. The results of these trials have demonstrated the efficacy of gefitinib that can be now considered as the standard first-line treatment of patients with advanced NSCLC harbouring activating EGFR mutations.

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Section: Development Of Gefitinib In “Unselected” Patientsmentioning

confidence: 99%

Gefitinib in Non Small Cell Lung Cancer

Costanzo¹,

Piccirillo²,

Sandomenico³

et al. 2011

BioMed Research International

Self Cite

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Advanced non-small-cell lung cancer with epidermal growth factor receptor mutations: current evidence and future perspectives

Costanzo

Montanino

Maïo

et al. 2013

Expert Review of Anticancer Therapy

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The identification of activating mutations in the tyrosine kinase domain of the EGF receptor (EGFR) predictive of response to tyrosine kinase inhibitors (TKIs) led to a therapeutic revolution in the treatment of patients with metastatic non-small-cell lung cancer (NSCLC). To date, eight randomized clinical trials have demonstrated that first-line treatment with TKIs in advanced NSCLC patients harboring activating EGFR mutations is associated with significant improvement in response rate, progression-free survival, quality of life and tolerability, compared with platinum-based chemotherapy. These results prompted the EGFR TKIs as the current standard first-line treatment of patients with advanced NSCLC harboring activating EGFR mutations. However, there are several questions that need to be addressed, including the best choice among different EGFR TKIs, the treatment of resistant disease and of patients with specific clinical conditions. Ongoing and future, well-designed trials should answer all these questions.

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Cetuximab in non-small-cell lung cancer

Carillio¹,

Montanino²,

Costanzo³

et al. 2012

Expert Review of Anticancer Therapy

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Cetuximab is a chimeric human-mouse anti-EGF receptor monoclonal antibody. In Phase I studies, no dose-limiting toxicities were observed with cetuximab as a single agent or combined with chemotherapy; pharmacokinetic and pharmacodynamic analyses supported 250 mg/m(2) weekly administration. Skin toxicity, diarrhea and fatigue were the most common toxicities. The positive results obtained in Phase II trials in patients with advanced non-small-cell lung cancer prompted two randomized Phase III trials evaluating cetuximab in addition to first-line chemotherapy. Both trials showed a small benefit in overall survival for the experimental treatment, which was considered insufficient by the EMA for marketing approval. However, a subgroup analysis of the FLEX Phase III trial recently demonstrated a larger survival benefit from the experimental treatment in patients with high immunohistochemical EGF receptor expression. This finding, if confirmed prospectively, could represent a new opportunity for positioning cetuximab into the standard treatment of advanced non-small-cell lung carcinoma.

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Methodological Issues of Clinical Research with EGFR Inhibitors

Cited by 3 publications

References 82 publications

Gefitinib in Non Small Cell Lung Cancer

Gefitinib in Non Small Cell Lung Cancer

Advanced non-small-cell lung cancer with epidermal growth factor receptor mutations: current evidence and future perspectives

Cetuximab in non-small-cell lung cancer

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