Routine Molecular Testing in Early NSCLC Post-Resection

Dr. Zofia Piotrowska: We're all adopters. Clearly, we've all drunk the Kool-Aid and I think are going to be continuing to offer this to our patients, but it really emphasizes the point of testing, and how critical testing is to these patients in the early-stage setting. And Gus, maybe as an interventional pulmonologist, I can bring you in because you're often the first point of contact for some of these patients. They may come in with a lung-screening CT, they may come in for a bronchoscopy, and so you're meeting them. What do you think about testing on that initial sample? Are you ordering it? Is it something that you're deferring to colleagues? And if so, what testing do you think should be done?

Dr. Gustavo Cumbo-Nacheli: Thank you for that question. The success of the treatment plan is directly proportional to the amount of time and conversation we have with the patient the first time we shake their hands. This is a high-level discussion with experts, and all of you provide treatment, whereas, maybe, the surgeon and I, we do the pre-treatment, which is diagnostic. The patient doesn't know when shows up in the clinic, what's going on, and what's going to happen. They don't know anything about personalized medicine or nodule risk gratification. So, at the very beginning, we have to prepare the patient that the biopsy is going to put a first name into the tumor they have, then there's testing that is going to put the last name. There's going to be waiting time in order to know what a preoperative treatment will be, and even if they were to have surgery, there may be other treatments that may happen before and after. So, communication with the patient is very important to secure the success of a program, and also, we discuss, well, there may be some testing that may happen after the initial biopsies. There are twice that we are going to have the opportunity of checking if there are any type of genetic rearrangements or DNA abnormalities that would allow for you to get a specific treatment that will be helpful for you. And obviously, we set the stage for them to go in-depth with discussions about different treatment options, and then, hopefully, they will be able to explain what true value care is provided to them, which is a good quality medication, better outcomes, and lower cost overall. So, we are openers for them to be closers, if you will, but it's very important that the first point of contact after a positive-screening CT, after a pre-resection, the pulmonologist or the interventional pulmonologist discusses that testing is coming. It may take a little while, but please, give us the time to get the chest set right in order for us to move forward.

Dr. Zofia Piotrowska: Such an important point, especially critical in that early-stage disease where patients are so eager to get to that next step. And Jay, you're often the next step in that journey for the patients as a thoracic surgeon. So, what testing are you checking to see? And maybe, specifically, what tests do you think need to be done here? Are you checking to see if they've been done on the biopsy? Are you ordering them on the resection specimen? So every institution, and geographically, everyone has a different workflow. What we do, at UCLA is to do reflexive NGS testing from the biopsy specimen. And often at the time of biopsy, we don't know what stage the patient has of- What stage of the non-small cell lung cancer the patient may have. So, the NGS testing has relevance, particularly, if the institution has clinical trials tied to targeted therapies in the early-stage setting. It has relevance in terms of efficacy or lack of efficacy with IO in the early-stage setting. And finally, to figure out which patients should go on ADAURA trial regimen, or which is now standard of care. So, the testing is critically important. I think there are two different sets of testing. One is the comprehensive NGS testing, both DNA and RNA. The other is, you want a quick turnaround on the PD-L1, the ALK, and the eGFR status. And they're mainly driven by IHC, but there are limited panels where you can get a quick turnaround on eGFR. So, right now we're in this kind of divisive situation where we're doing both NGS testing that takes a couple weeks, and then the quick turnaround test that we need to act upon right away.

Dr. Ashish Saxena: Oh, I was going to say- I think what Jay's saying is true, especially about the quick-turnaround times because we do have that other option of neoadjuvant chemoimmunotherapy, but it's not really for patients that have the eGFR or ALK mutation. So, getting that information sooner rather than later so we know what to do with them is really important.

Dr. Zofia Piotrowska: It's such an important point, and I think it is really important to keep in mind that in CheckMate816, the patients with eGFR and ALK alterations were excluded from that study. And even though we are starting to see now more studies where that, maybe, wasn't necessarily the case, I think we would all agree that if we have a patient that has a known eGFR mutation, chemo IO is not the right neoadjuvant therapy for them. And we can talk about, whether is there a right neoadjuvant therapy for them or should it be adjuvant. But I think what is clear right now is that those patients should not go on chemoimmunotherapy. And you can only make that decision if you do the testing. And so, I totally agree. I think getting that done right away is so very important.