Treatment Regimen for Patients With ALK+ Non-Small Cell Lung Cancer - Episode 4
Jonathan W. Riess, MD, MS:At the time of progression, an important question is whether or not to doALKmutation testing to try to find the mechanism of resistance to an ALK TKI, and that’s something I generally do. So, with the standard of care now being alectinib in the first-line treatment, the next step can sometimes be driven by theALKresistance mechanism.
Now, the standard of care after progression on alectinib would generally be platinum-based chemotherapy. And immunotherapy, such as PD-1 antibodies, now pembrolizumab, nivolumab, and so forth have been studied in these patients and response rates are generally very low. So, that’s something I don’t consider until way later lines of therapy. The standard treatment, without having a resistance mutation, I would consider to be platinum-based chemotherapy.ALKresistance mutations can sometimes point in the direction of a clinical trial.
For example, one of the resistance mechanisms to alectinib is the G1202R mutation, and responses have been shown to lorlatinib and other further next-generation ALK inhibitors with those drugs. It’s unclear whether brigatinib and ceritinib and those drugs could be sensitive when there’s progression on alectinib. There’s a certain spectrum ofALKmutations that we know, based on the IC50 in cell culture, where certain ALK inhibitors may have more activity than others. By identifying what those mutations are, you could potentially match to another ALK TKI, either approved or in a clinical trial, to try to treat the patient. So, that’s something that I do. But the standard of care right now after progression on first-line alectinib remains platinum-based chemotherapy. But I would strongly consider for physicians who are treating these patients to seek out and help find clinical trials, such as lorlatinib and other next-generation ALK inhibitors, that may have activity against the spectrum of resistance mutations.
Transcript edited for clarity.
CASE:ALK+ NonSmall Cell Lung Cancer