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INTRODUCTION

A leading cause of mortality, lung cancer is the second most common cancer type found in the United States. In 2015, an estimated 22 200 new patients were diagnosed, while more than 158 000 lung cancer deaths were reported, a mortality rate exceeding that of breast, prostate, and colorectal cancers combined. The 5-year survival rate, although rising in recent years, remains a low 17.4%.¹

Characterized by heterogeneous histological and morphological features, lung cancer is divided into 2 broad classes: the more common non-small cell lung cancer (NSCLC), which accounts for 86% of cases, and small-cell lung cancer (SCLC). NSCLC is further segmented into 3 histological subtypes according to the tumor's biological characteristics and cell of origin: adenocarcinoma, squamous-cell carcinoma, and large-cell bronchoalveolar carcinoma, which some specialists now reclassify as either adenocarcinoma or neuroendocrine tumor depending on its genotyping.^2-3 Adenocarcinomas, which are located in the lung periphery, are most often seen in non-smokers, while squamous-cell carcinomas have a central location, are slow growing, and have a clear relationship to smoking history.⁴ The recognition that NSCLC is not a single disease but rather a collection of distinct pathologies has changed the therapeutic approach from one based on intravenous chemotherapy to another determined by histology, molecular selection, and performance status (PS).⁵ Tumor screening for a number of prognostic biomarkers, which predicts the sensitivity and potential response to targeted therapy, is now considered essential to the optimal management of patients with NSCLC.^5-6 The discovery of mutations in epidermal growth factor receptor (EGFR) and the abnormal fusion of the anaplastic lymphoma kinase (ALK) and other receptor tyrosine kinases has led to the development of novel first-line targeted therapies such as erlotinib, gefitinib, and crizotinib^7-9; second-generation targeted therapies afatinib, ceritinib, and alectinib^10-12; as well as a third-generation osimertinib.¹³ These tyrosine kinase inhibitors (TKIs), which have helped individualize the treatment of patients with NSCLC, have become first-line therapies for patients with adenocarcinoma and large-cell histology patients whose tumors express these alterations (15% for EGFR-positive mutation and 4% for ALK rearrangement) and for whom targeted agents are more effective than conventional chemotherapy. An additional approach, the immunoglobulin G1 monoclonal antibody necitumumab, also blocks the binding of EGFR and its ligands. This drug is approved for initial therapy for EGFR-positive, advanced NSCLC of squamous histology patients only.¹⁴

This educational activity will explore the role of the key molecular markers now used in the screening of NSCLC patients, particularly those with adenocarcinoma and large-cell tumors, and the current and emerging biologic drugs targeted to them. Finally, it will examine the pharmacist's perspective in implementing individualized therapeutic regimens for patients.