ALK Gene Rearrangements As A Therapeutic Target in Non-small Cell Lung Cancer - Episode 1

Overview of ALK+ NSCLC


Karen Reckamp, MD, provides an overview of ALK gene rearrangements and their clinical significance in patients with advanced NSCLC.

Karen Reckamp, MD: Hello and thank you for joining this Targeted Oncology™ presentation titled, “ALK Gene Rearrangements as a Therapeutic Target in Non–small Cell Lung Cancer.” I’m Karen Reckamp, professor of medicine, and director of the Division of Medical Oncology at Cedars-Sinai Medical Center in Los Angeles, California.

Joining me today is my esteemed colleague, Dr Jyoti Patel. I would like to invite Dr Patel to introduce herself.

Jyoti Patel, MD: Hi, thank you, Dr Reckamp. I’m Jyoti Patel, professor of medicine at Northwestern University [Chicago, Illinois,] and the Robert H. Lurie Comprehensive Cancer Center, and associate chair for clinical research at the medical school. Thank you for having me.

Karen Reckamp, MD: The treatment of anaplastic lymphoma kinase, or ALK, rearrangement-positive advanced non–small cell lung cancer remains a challenge. In today’s Precision Medicine in Oncology® discussion, we will talk about the role of ALK gene rearrangements in non–small cell lung cancer growth and progression, and review the mechanism of action and safety and efficacy data from recent trials of agents that target ALK gene rearrangement-positive advanced non–small cell lung cancer.

I’ll start with an overview of ALK-positive non–small cell lung cancer. Overall, this occurs in about 4% of non–small cell lung cancers, and the alteration was first reported in non–small cell lung cancer in 2007. The typical patient with ALK-positive non–small cell lung cancer is generally younger, more often with adenocarcinoma histology, though this can occur in other histologies, and generally these occur in light or never smokers. There’s not a significant regional difference as we see with EGFR-positive non–small cell lung cancer. We don’t see that same regional difference with ALK-positive non–small cell lung cancer.

ALK in normal pathophysiology is important for cell differentiation and proliferation, and when ALK rearrangements occur, there’s a fusion protein that results in a constitutively active tyrosine kinase that causes unchecked cell growth and proliferation to generate tumor genesis for non–small cell lung cancer. There are many types of ALK rearrangements, the most common is EML4-ALK. But there are many ALK rearrangements, and even within EML4, there are several variants that we can see. Fortunately, for patients who are diagnosed with ALK non–small cell lung cancer, there are several very effective drugs that we’ll be talking about today. This means that even for patients with advanced disease, the median survival is around 5-plus years. Though this is not as good as we’d like it to be, it’s still impressive for advanced disease in non–small cell lung cancer.

Transcript edited for clarity.