EGFR Testing for Metastatic Non-Small Cell Lung Cancer with Jonathan W. Riess, MD, MS: Case 1 - Episode 6
Jonathan W. Riess, MD, MS: In terms of defining progression, in clinical trials we use the RECIST criteria, which is essentially any new non-target lesion or 20% or greater growth of a target lesion. But, in your typical clinical practice, it’s more of a subjective call. If you look at the NCCN Guidelines in terms of gauging whether to switch therapy, because that’s really what you’re looking at, it discusses dividing patients into symptomatic versus asymptomatic. Now, obviously a lot of us don’t wait for patients to develop worsening shortness of breath before switching them over. We like to try to get a response and get benefit before it gets to that point. So, some of the things that I look at is the bulk of disease and the tempo of disease, and I think most oncologists look at that as well.
I think about switching therapy based on progression when there’s a high bulk of disease, when they’re symptomatic consistent with the NCCN Guidelines, and when you get a scan and it looks like there’s rapid growth because it’s suggesting the tempo is picking up. And, in those patients, in terms of your practical experience outside of a clinical trial, those are the ones I look at in terms of thinking about switching to a new therapy. I have several patients who have a great response and then they plateaued on these EGFR inhibitors, for example. You get a scan 2 months later and there’s a millimeter or 2 of growth. And I’ve had some going on for a year or so where each scan there’s like a millimeter or 2 of growth, but over a year, it’s maybe half a centimeter or a centimeter. Those I typically follow closely with scans, and watch them very carefully for symptoms. Those are the main things I look at: symptoms, tempo of disease, and bulk of disease. And, I think the majority of oncologists look at those as well, in terms of making practical day-to-day decisions for patients outside of clinical trials.
The use of osimertinib for the treatment of T790M-positive nonsmall cell lung cancer has changed the paradigm in terms of detecting by looking at resistance mechanisms at the time of progression on erlotinib, afatinib, or gefitinib; approved first-line EGFR TKIs. And, because it has a response rate of about 60% and a median progression-free survival of 9.6 monthswhich really highlights the clinical activity of this drug in patients with EGFR T790M-positive non–small cell lung cancer—we know that based on the clinical trials, if they’re T790M-negative, the response rates and the progression-free survival are much lower. It’s not as clinically active. So, now that we have a treatment to match to the T790M mutation, it’s become essentially standard of care. And that’s reflected in the NCCN Guidelines, to take a look at the mechanism of resistance at the time of progression to try to match to this drug. Previously, these resistance mechanisms were mainly looked at as part of clinical trials and more academic questions. But, now that we have an approved therapy, it’s really changed and evolved to standard of care.
Riess case 1:
A 44-year-old female with relapsed stage IV adenocarcinoma.