Systemic therapy of advanced non-small cell lung cancer: Major-developments of the last 5-years
Introduction
Lung cancer is the second most common cancer in men and women and a leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) representing approximately 85% of all cases.1 More than half of the patients are still diagnosed with advanced metastatic, disease and have a poor prognosis.2 Platinum-based palliative chemotherapy is considered a standard therapy for advanced disease, resulting in a median survival of 8–10 months with only 5% patients alive at 2 years.3 A recent randomised trial4 highlighted the importance of early palliative care given these poor outcomes. Patients assigned to early palliative care had a better quality of life (QoL) and lived longer compared to patients on standard care (which in most of the patients includes chemotherapy) alone.
Even though, some patients benefit from chemotherapy, the result of the ‘one size fits all’ approach to treatment in NCSLC is finally changing. During the last few years we have learnt that by tailoring chemotherapy according to tumour histology and/or the response to the first four cycles of chemotherapy, the results obtained by standard chemotherapy can be improved upon. Recent improved understanding of the molecular biology of NSCLC has been followed by new, targeted therapies, and represents a major step forward in the treatment of this disease. This review presents the most recent relevant progress in systemic anti-cancer therapy of advanced NSCLC and delineates today’s new treatment options.
Section snippets
Platinum-based chemotherapy
The meta-analysis published in 1995 established the benefit of chemotherapy compared with supportive care alone (without chemotherapy) for advanced NSCLC.5 The updated meta-analysis, published in 2008 assessing newer platinum-based regimens incorporating third-generation cytotoxic drugs (gemcitabine, vinorelbine and paclitaxel), showed a further chemotherapy benefit (23% reduction of risk of death, 1-year survival gain of 9% and 1.5 months absolute increase in median survival).6 The results
Epidermal growth factor receptor (EGFR)-directed therapy
The major advances in the treatment of NSCLC during the last 5 years are due to the discovery of activating EGFR mutations as well as the introduction of reversible tyrosine kinase inhibitors (TKIs) of EGFR in all lines of treatment of EGFR mutated disease. First-generation EGFR TKIs, gefitinib and erlotinib, were initially studied in unselected populations of NSCLC patients in which they have demonstrated modest activity in second- and third-line treatment.36, 37, 38 The predictive value of
Conclusions
During the last 5 years major advances have been made in individualising systemic therapy for advanced NSCLC. The standard chemotherapy can already be tailored based on tumour histology, with pemetrexed being effective mainly in patients with non-squamous-cell histology. Overall survival benefits in maintenance chemotherapy are dominated by pemetrexed results in the switch or continuing maintenance setting. Major developments in NSCLC biology and identification of druggable targets, such as EGFR
Conflict of interest statement
None declared.
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