Abstract
To provide consensus recommendations on the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIS) in patients with advanced or meta-static non-small-cell lung cancer (NSCLC). Using a systematic literature search, phase II trials, randomized phase III trials, and meta-analyses were identified for inclusion. A total of forty-six trials were included. Clear evidence is available that EGFR-TKIS should not be administered concurrently with platinum-based chemotherapy as first-line therapy in advanced or metastatic nsclc. Evidence is currently insufficient to recommend single-agent EGFR-TKIS as first-line therapy either in unselected populations or in populations selected on the basis of molecular or clinical characteristics. Following failure of platinum-based chemotherapy, the evidence suggests that second-line EGFR-TKIS or second-line chemotherapy result in similar survival. Quality of life and symptom improvement for patients treated with an EGFR-TKI appear better than they do for patients treated with second-line docetaxel. Sequence of therapy may not appear to be important, but if survival is the outcome of interest, the goal should be to optimize the number of patients receiving three lines of therapy. Based on available data, molecular markers and clinical characteristics do not appear to be predictive of a differential survival benefit from an EGFR-TKI and therefore those factors should not be used to select patients for EGFR-TKI therapy. The EGFR-TKIS represent an additional therapy in the treatment of advanced or metastatic NSCLC. The results of ongoing clinical trials may define the optimal role for these agents and the effectiveness of combinations of these agents with other targeted agents.
Highlights
Lung cancer represents a major health burden in Canada
What is the role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) as first-line therapy of advanced or metastatic non-small-cell lung cancer (NSCLC) as a single agent or in combination with chemotherapy?
Results of the BR.21 and ISEL trials demonstrated that erlotinib (2.2 months vs. 1.8 months) and gefitinib (3.0 months vs. 2.6 months) significantly prolong time to disease progression 56,57
Summary
Lung cancer represents a major health burden in Canada. 23,300 new lung cancer cases and 19,900 deaths from lung cancer occurred in 2007, most of which were non-small-cell lung cancer (NSCLC). 23,300 new lung cancer cases and 19,900 deaths from lung cancer occurred in 2007, most of which were non-small-cell lung cancer (NSCLC)1 Most of these patients either present with or develop metastatic disease at some point during their illness; potentially, they are candidates for systemic therapy approaches such as chemotherapy. Publication of the Non-small Cell Lung Cancer Collaborative Group meta-analysis in 1995 established the association of first-line platinum-based chemotherapy with a modest improvement in survival for patients with metastatic disease 2. The introduction of newer drugs such as vinorelbine, gemcitabine, paclitaxel, and docetaxel have resulted in further small improvements, most patients still experience disease progression within a short time, with a median time to progression (TTP) of approximately 4 months 3–5
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