Lowell L. Hart, MD
Frontline therapy for patients with ALK
-positive non–small cell lung cancer (NSCLC) is poised to change in the coming years, as researchers continue to explore agents beyond crizotinib (Xalkori).
“[The ALK-positive population] is sort of a small percentage of the patients with adenocarcinoma of the lung,” said Lowell L. Hart, MD, during an interview at the 2016 OncLive
State of the Science Summit on Advanced Non–Small Cell Lung Cancer. “It’s small but very important, because there have been huge breakthroughs in treating these patients with tyrosine kinase inhibitors—oral agents that specifically target this translocation.”
Aside from the other approved ALK inhibitors ceritinib (Zykadia) and alectinib (Alecensa) in the post-crizotinib, second-line setting, the FDA recently granted a priority review designation to brigatinib for patients with metastatic ALK
-positive NSCLC who are resistant to crizotinib.
In his interview, Hart, who is scientific director of Research at Florida Cancer Specialists and Research Institute, and associate professor of Internal Medicine at Wake Forest School of Medicine, discussed the available and emerging targeted therapies in ALK
-positive NSCLC and challenges that remain in this setting.
OncLive: What are the recent advances in ALK-positive NSCLC?
: The biggest one was a few years ago when crizotinib was approved. This is a drug that specifically hits this molecular defect and it made a tremendous difference. Studies have shown that compared with giving those patients chemotherapy, they actually do better if they are given this pill versus the standard therapy in first-line or second-line settings.
We have also had the development in the last 2 years of 2 other agents that are already on the market right now. These drugs are ceritinib and alectinib. These are both drugs that have come out. They also have the advantage of targeting metastases in the brain and they have a better penetration into the brain. This is a common problem in these patients. They can have brain metastases either at diagnosis or soon after.
Are there other agents that are being investigated in this area?
There are several other agents in the pipeline. Some are from small companies. One is called brigatinib that was presented recently at the 2016 ASCO Annual Meeting, which looks pretty exciting.
The second-generation ALK-inhibitor agents, and others coming along, are very exciting. They have some advantages with decreased toxicity and certainly with improved penetration of the central nervous system, as compared with the first-generation drugs.
What should community oncologists take away from your lecture?
The number 1 point is to be sure that all of your patients with adenocarcinoma of the lung are tested to see if they have an ALK
abnormality driving the cancer. The word has gotten out now to most medical oncologists that we need to look for these driver mutations.
The most common of them is EGFR
, but ALK
are sometimes overlooked. However, it is equally important to find those patients. This is because these agents can have a tremendous improvement on their quality of life and, potentially, on their survival if these patients are found and appropriately treated with the new agents.
What looming issues still need to be addressed?
The biggest challenge is getting enough tissue so that all of these tests can be done appropriately. Lung cancers frequently have small amounts of tissue available. Sometimes, it is almost necessary to go back and rebiopsy just to get enough tissue to do the testing. It’s important to remember that it is not adequate to treat a patient anymore with a nonsquamous carcinoma of the lung without knowing their ALK
status, at a minimum. We actually like to look for other potential driver mutations, whenever possible.