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A Disease State Update on ALK-Positive NSCLC (Sponsored)

Executive Summary

The most common cause of cancer-related mortality in the United States is lung cancer, about 80-85% of which is non-small cell lung cancer (NSCLC). The management of NSCLC has evolved substantially owing to the discovery of molecular drivers of cancer growth as well as the development of medications that specifically target actionable driver mutations to personalize therapy. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase target implicated in NSCLC, and therapies targeted to- ward ALK have improved disease outcomes for patients with ALK-positive NSCLC. However, unmet needs re-main. It is important to identify patients with ALK rearrangements who may benefit from targeted therapy, but molecular testing to determine ALK status is currently underperformed in real-world practice. Treatment with ALK inhibitors is not curative, owing to a variety of genetic mechanisms of acquired resistance. Next-generation ALK inhibitors have begun to address this challenge, with activity against secondary resistance mutations as well as better control of central nervous system metastases, but optimal sequencing of ALK inhibitor therapy still needs to be determined. This report will help oncology care providers understand the significance of ALK gene rearrangements for NSCLC, the importance of performing molecular testing in patients with metastatic NSCLC to guide treatment decision-making, the drivers of acquired resistance to ALK inhibitors, and the potential benefits of ALK inhibition in relapsed or refractory settings.

This report was developed by HMP with support from Takeda Oncology. Takeda is acknowledged for participating in the writing, review, and editing of this report.

 

Introduction

Lung cancer is the most common cause of cancer-related mortality in the United States, representing about 20% of cancer mortality as a whole.1 About 234,000 new cases of lung cancer will be diagnoses in the United States in 2018, with an estimated 154,000 deaths from lung cancer the same year.2 About 80% to 85% of lung cancers are non-small cell lung cancer (NSCLC).3 NSCLC's three primary histologic subtypes include squamous cell, adenocarcinoma and large cell, with adenocarcinoma being the most common.4

The management of NSCLC has evolved substantially owing to the discovery of molecular drivers of cancer growth as well as the development of medications designed to specifically target actionable driver mutations to personalize therapy. NSCLC is highly heterogenous, with a number of oncogenes including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), Kirsten rat sarcoma viral oncogene (KRAS), and V-raf murine sarcoma viral oncogene homolog B1 (BRAF). One study reported that actionable driver mutations were found in 64% of tumors from lung cancer adenocarcinomas.5 Targeted treatment of oncogenic drivers with tyrosine kinase inhibitors (TKI) have led to better patient outcomes versus chemotherapy and may improve quality of life.5

Next: ALK Rearrangements in NSCLC and Implications for Treatment

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