Testing for ALK Rearrangements in mNSCLC

Jonathan W. Riess, MD: In terms of the available testing for ALK-rearranged non–small cell lung cancer, you have a couple of options. One is broad-based genomic profiling with next-generation sequencing, which is typically what I send out because it enables us to at least initially get an identification of trying to find different mutations that you can match to targeted therapies rather than focusing on 1. ALK FISH [fluorescence in situ hybridization] and ALK IHC [immunohistochemistry] are also methods that are used.

ALK IHC and FISH may have a quicker turnaround time. Sometimes, if I really suspect ALK, for example, they can be associated with pericardial effusions, pleural effusions. I’ve had patients with that. You send off an ALK IHC and potentially get that and intervene quicker. We have had cases like that at our institution. That could be done as either a standalone or screening test, followed by confirmation, which is approved as a standalone as well.

Those are the different methods used. In terms of using circulating tumor DNA [ctDNA], I often send that out if I need a quick result because that may come back faster than looking at tissue biopsy or repeat tissue biopsy, or if you think there may be insufficient tissue. Sometimes, there’s not enough circulating tumor DNA being shed in the blood where a negative test doesn’t disprove it. It could be a false negative, where tissue is important, but those are the techniques that I use. There are some folks that think more about RNA-based methodologies that may be more accurate in detecting ALK fusions, but the general standard is broad-based genomic profiling with next-generation sequencing.

Lyudmila A. Bazhenova, MD: In my institutions, I have options. I can choose my own next-generation sequencing, or I can send it to a reference company. I test all my patients with nonsquamous, non–small cell metastatic for ALK rearrangement and other rearrangements we’ve discussed. I also test my patient’s squamous cell carcinoma if they have certain phenotypic characteristics. If I see a patient with squamous cell carcinoma who was a nonsmoker, or if I see patients with squamous cell carcinoma who have a small biopsy on FNA [fine needle aspiration], which made the basis for the diagnosis for those patients, it is certainly possible that you’re dealing with what’s called a mixed histology or adenosquamous lung cancer. Those patients can harbor ALK rearrangements. If you remember, the first patient with ALK rearrangement described by Dr [Manabu] Soda was a patient with squamous cell carcinoma, so for a certain subset of patients with squamous cell carcinoma, I do test for ALK.

Balazs Halmos, MD: B-FAST is a very interesting study. We participated in it at our institution. It utilizes ctDNA testing up front to allow quick introduction of targeted agents or immunotherapeutic drugs dependent on findings. It is easy to force the integration of that into our practices since we use ctDNA already. In a way, it will be a very smooth transition toward practice. The study has shown that if you use ctDNA and the type of ALK alterations in ctDNA, you can offer alectinib with a great chance of success.

This really confirms the paradigm that we’ve seen from other studies, especially for EGFR—for example, in FLAURA2, we could see that ctDNA-detected EGFR alterations yield excellent outcomes in terms of EGFR targeting, similar to what we see with tissue-based testing. This will be a slam dunk in terms of incorporating into our practices for the care of our patients.

Transcript Edited for Clarity