Importance of Biomarker Testing for RET in Non Small Cell Lung Cancer - Episode 8

Effect of NGS Wait Time on Decision Making


Robert Doebele, MD, PhD: Turnaround time for next-generation sequencing in our patients with lung cancer is really a critical factor. If a patient has very aggressive disease, with a heavy symptom burden, many physicians may feel that it's difficult to wait for next-generation sequencing results to come back. And I think it's critical that those turnaround times for next-generation sequencing be shortened.

Now, there have been some recent developments, I think, that can help us significantly in terms of turnaround time. For example, ctDNA testing, circulating tumor DNA testing, has a turnaround time of approximately 1 week for many assays. So that significantly shortens some of the tumor-based testing that can take 10 days to 3 weeks. One of the issues relating to ctDNA testing is that it can have lower sensitivity.

But the way that I look at this is, I typically will send both ctDNA testing or blood-based testing as well as tumor testing. If the ctDNA is positive, I feel very comfortable treating off of those results based on a positive oncogene test. If it's negative, I think you still need to wait for the tumor testing if that patient can afford to wait. And really, in my clinical practice, I’ve found that a lot of this is managing anxiety.

If the patients have a modest disease burden, are not particularly symptomatic, I think talking through with the patient the potential benefits of waiting for that tumor testing to come back is critical to put their mind at ease and explain why we want to wait for the best therapy because we could, in theory, do harm if were treated, for example, only off of a PD-L1 [programmed death-ligand 1] test that's high in a never smoker. I think there's a very low chance that that patient is going to respond to that therapy, and they may actually end up having very rapid progression and symptomatic deterioration due to rapid progression.

There are no subgroups of patients for whom I would not do next-generation sequencing on. However, if a patient is very symptomatic, we may have to initiate therapy right away. I would still want to initiate testing, though, so that once we've initiated whatever aggressive therapy were going to pursue, that we have another option for when that therapy fails or if they're not tolerating that therapy.

In summary, we really should be testing all patients. It may be that we cannot wait for the testing results to come back on a small proportion of our patients who have a heavy disease burden and are very symptomatic. However, we still want that testing because it's going to allow us the treat those patients with effective therapies later on down the road.

I think it's critical to explain to our patients why testing is so important. A significant proportion of our patients now, roughly 10% to 15% of our patients, are EGFR positive, 5% are ALK, 1% to 2% are ROS1, and 3% are BRAF mutation positive; 1% to 2% are RET gene fusion positive. That really is starting to add up to a significant number of patients who have meaningful therapies available to them.

I think taking the time to explain to them that these therapies are often far superior to standard of care chemotherapy or chemotherapy plus immunotherapy with far less toxicity helps patient anxiety and helps them understand why we're waiting. The other thing that we're able to do with our patients is do close monitoring. If a patient is perhaps borderline with moderate tumor burden and some symptoms, one thing to do is initiate testing with a backup plan that we're going to start chemotherapy if the results don't come back fast enough.

But have close contact with that patient. Tell them the types of symptoms that we’re monitoring for that we don't feel can wait for further testing to come back. And I think all of those conversations will help the anxiety of the patient, help them understand why we want to wait so that we can give them the best and most appropriate therapy for their cancer.

Transcript Edited for Clarity