Genetic profiling and epidermal growth factor receptor-directed therapy in nonsmall cell lung cancer

Abstract

The principle of preferentially selecting patients most likely to benefit from therapy according to their genetic profile has led to substantial clinical benefit in some tumour types, and has potential to considerably refine treatment in advanced nonsmall cell lung cancer (NSCLC). Effective, reliable use of molecular biomarkers to inform clinical practice requires the standardisation of testing methods and careful assessment of biomarkers’ predictive and prognostic value.Although a number of studies have shown that patients with activating mutations in exons 18–21 of the epidermal growth factor receptor (EGFR) gene respond particularly well to gefitinib and erlotinib, a prospective, randomised study was needed to differentiate between the prognostic and predictive value ofEGFRmutations. From one such study, it appeared that mutational testing should become standard at diagnosis, at least for adenocarcinoma patients with a never or low smoking history, as clinical predictors are insufficient to optimise treatment.However, outstanding questions remain: what are the treatment options for patients with tumours resistant to erlotinib/gefitinib? What conclusions about treatment can we draw fromEGFRcopy number orKRASmutation status? What role should anti-EGFR antibodies play in NSCLC treatment, and in which patients?This review considers current evidence linking biomarker profile to efficacy of EGFR-targeted therapy in NSCLC, and clinical implications of recent findings.

Cost-effectiveness of three strategies for second-line erlotinib initiation in nonsmall-cell lung cancer: the ERMETIC study part 3

“…However, these analyses were retrospective and limited by sample availability. It has since been established that EGFR mutation status influences the efficacy of EGFR tyrosine kinase inhibitors in both first-and second-line settings [15][16][17][18].…”

Erlotinibversuscarboplatin and paclitaxel in advanced lepidic adenocarcinoma: IFCT-0504

“…However, the low EGFR mutation rate (n=5, 5.6%) indicates that this molecular alteration only minimally impacts the treatment efficacy, even in arm E. DCR and PFS were not affected by tumour KRAS mutation status (table 2). Given that KRAS mutations were observed in only seven of the 41 tumours in arm E patients, this finding cannot account for erlotinib's low efficacy in mucinous patients [30]. TUBB3 and MSH2 are markers that have previously been revealed to demonstrate positive expression in adenocarcinoma [21,22].…”

Predictive biomarkers in patients with resected non-small cell lung cancer treated with perioperative chemotherapy

“…For lung cancer the only biomarkers reaching a significant predictive effect for a targeted therapy, as compared with chemotherapy, are epidermal growth factor receptor (EGFR) mutations [9,10] and anaplastic lymphoma kinase (ALK) rearrangements [11] in oncogene-driven tumours, representing ,15% of metastatic NSCLC. Indeed, five prospective phase III trials in Asian and Caucasian populations clearly showed that EGFR kinase inhibitors (erlotinib, gefitinib or afatinib) were superior to cisplatin-based chemotherapy in the first-line setting in patients with EGFR activation mutations [9,[12][13][14][15].…”