The Role of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors as Therapy for Advanced, Metastatic, and Recurrent Non-Small-Cell Lung Cancer: A Canadian National Consensus Statement

Abstract

PurposeTo provide consensus recommendations on the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced or metastatic non-small-cell lung cancer (NSCLC). MethodsUsing a systematic literature search, phase II trials, randomized phase III trials, and meta-analyses were identified for inclusion. ResultsA 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. ConclusionsThe 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. KEY WORDSNon-small-cell lung cancer, targeted therapy, epidermal growth factor receptor, tyrosine kinase inhibitor, molecular marker

Histopathological and immunohistochemical features associated with clinical response to neoadjuvant gefitinib therapy in early stage non-small cell lung cancer

“…Among ADC patients, better response rate was also reported in tumors with prominent lepidic (formerly bronchioloalveolar carcinoma or BAC) growth pattern [5,6]. However, molecular studies have demonstrated that the presence of mutations in the tyrosine kinase domain (TKD) of the EGFR gene is a better predictor of response than ADC histology [4,7,8]. In contrast, epithelial-mesenchymal transition (EMT) is a potential marker of resistance to EGFR TKI therapy [9,10].…”

“…Higher response rates to EGFR TKI therapy have been observed in NSCLC patients who are East Asian, never-smokers, female or present with adenocarcinoma (ADC) histology [1,3,4]. Among ADC patients, better response rate was also reported in tumors with prominent lepidic (formerly bronchioloalveolar carcinoma or BAC) growth pattern [5,6].…”

Usefulness of tissue microarrays for assessment of protein expression, gene copy number and mutational status of EGFR in lung adenocarcinoma

“…Together, these two mutations account for almost 90% of all EGFR mutations in NSCLC [20]. Response rates to EGFR-TKIs range from 48% to 90% for patients with EGFR mutations, while responses are less common in patients without a mutation (5-31%) [21]. Interestingly, two mutant-specific antibodies directed against the most common mutant forms of the EGFR oncoprotein have been recently developed for IHC use: 15-bp deletion (E746_A750del) in exon 19 and the L858R point mutation in exon 21 [22].…”

Design, synthesis and biological activities of novel oxazolo[4,5- g ]quinazolin-2(1H)-one derivatives as EGFR inhibitors

“…4.1.5.3.12. 8-(3, 4-Dimethoxyphenylamino)-1-(2-methoxyethyl) oxazolo [4,5-g] 3.29 (3H, s); 13 C NMR (125 MHz, d: 157.34, 153.50, 148.46, 147.02, 146.04, 145.58, 132.27, 130.71, 115.19, 111.84, 111.66, 108.71, 106.49, 100.57, 67.66, 58.08, 55.74, 55.60, 41.90. 4.1.5.3.13.…”