David C. Portnoy, MD
Ongoing clinical trials are investigating targeted agents for KRAS, MET,
mutations in non–small cell lung cancer (NSCLC). As more mutations are identified, the treatment landscape continues to shift away from chemotherapy regimens and toward biomarker-driven approaches, some of which include targeted agents plus immunotherapies, explains David C. Portnoy, MD.
The combination of targeted agents and chemotherapy have not been able to delay resistance in patients with lung cancer, says Portnoy. Although identifying targeted agents and driver mutations have been a focus of research, he predicts that down the line, the treatment landscape is “going to focus on immunotherapy and how it interplays in situations in which we have an identifiable driver mutation and a drug that can treat that mutation. We’ll have to determine how to incorporate the benefits of immunotherapy into those situations.”
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Advanced Non–Small Cell Lung Cancer, Portnoy, a hematologist and medical oncologist at West Cancer Center, assistant professor of medicine at Nova Southeastern College of Osteopathic Medicine, the University of Tennessee Health Science Center, discussed emerging developments with targeted agents in lung cancer.
OncLive: How has the identification of ALK, EGFR, and other molecular markers helped drive treatment in NSCLC?
In the past, all NSCLCs were treated exactly the same. Histology didn't matter and molecular underpinnings with a cancer didn't matter; they all were treated with chemotherapy whether you had squamous cell disease or adenocarcinoma. Everyone knows how chemotherapy makes patients feel, and of course there are the toxicities and limitations of chemotherapy. With chemotherapy alone, life expectancy for some metastatic NSCLCs is generally under 1 year.
Now, we are realizing that, in many of these cases, we can identify specific mutations that are driving the cancer. We're developing drugs that attack those specific mutations, allowing us to pinpoint the exact cause, or driver, of the cancer. This leads us to more efficiently attack the cancer with better results and fewer side effects.
We know about testing for ALK, EGFR, ROS1, and BRAF. What are some other emerging molecular targets?
Typically, we test a very wide panel of targets. Unfortunately, our testing is better than our treatments. We have treatments for EGFR, ALK, ROS1, BRAF,
; however, unfortunately there are a lot of mutations that we don't necessarily have great treatments for yet. There are many targeted agents that are still in the clinical trial stage such as for KRAS, MET,
What is the prevalence of these mutations, and what does the development look like in terms of targeted agents for them?
is the most common driver mutation seen in NSCLC. It comprises about 25% of NSCLC cases in which a driver mutation can be identified. We're still in the clinical trial stage, and there haven't been too many promising leads yet.
Please expand on what clinical research is needed in this setting.
You first want to identify targets and then identify the drugs that match and attack the target better. You’ll always find that there is a limit to how good it can be because of acquired resistance. Then, we’ll figure out why resistance develops and come up with another drug to meet the resistance.