Erminia Massarelli, MD, PhD
The November 2017 FDA approval of the ALK inhibitor alectinib (Alecensa) for the frontline treatment of patients with ALK-positive non–small cell lung cancer (NSCLC) quickly changed the standard of care. But ongoing research suggests that other ALK inhibitors are also poised to significantly impact this patient population.
-positive NSCLC based on recent regulatory decisions and what additional advancements are expected in the year ahead.
OncLive: Please provide an overview of your presentation on targeted therapies for ALK-positive NSCLC.
: ALK-mutated NSCLC [makes up a small percentage] of all NSCLCs, and they are presented in a very selected group. They are usually associated with a never smoking history and a young patient population, and are generally diagnosed at metastatic stage. The treatment of [patients with] ALK-translocated lung cancer has been completely changed by our ability [to develop] ALK inhibitors.
How has the FDA approval of alectinib changed this landscape?
Today, we have a new standard first-line treatment, which is alectinib and is indicated for patients with brain metastases. In fact, in a clinical trial, there was a head-to-head comparison between alectinib and crizotinib. Patients who received alectinib had better progression-free survival than those who got crizotinib. In particular, the development of brain metastases was much lower in the alectinib arm versus the crizotinib arm.
In addition, the side effect profile is better for alectinib when compared with crizotinib and ceritinib (Zykadia). Alectinib is a drug easily managed in patients and it allows for patients to have fewer breaks on therapy.
What other inhibitors are showing promise in the pipeline?
We are seeing change in our practice for the first-line setting. Unfortunately, patients eventually develop resistance to ALK inhibitors, even the new-generation inhibitors, and there are many other ALK inhibitors that are being developed. Among those, there are brigatinib and lorlatinib, and they actually have different [levels of] efficacy in different mutations.
Lorlatinib looks like, at least from preclinical data, to have activity in the majority of known ALK mutations. We are waiting on more [data on] this third-generation ALK inhibitor. As of today, we know that first-line alectinib is effective and then next-generation ALK inhibitors are the ones that are promising as second- and third-line therapies. In addition, it is possible to use crizotinib and ceritinib (Zykadia) later on if you have the choice of these drugs.
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