David R. Spigel, MD, FASCO, on NSCLC Treatment Planning: Role of 14-Gene Molecular Assay

We are discussing a trial we presented here at ASCO. It's a late-breaking abstract. It's called the AIM-HIGH study. The goal of this trial was to see if we could help patients with early-stage lung cancer live longer without their cancer coming back. Early-stage lung cancer is certainly a setting where we want to cure patients, and historically we divide early stages into stages 1, 2, and 3. Lung cancer, non-small cell lung cancer, and chemotherapy is an established treatment in stage 2 and in 3 disease after surgery, and stage 1 and in some stage 2 cancers. It's still something you can be on the fence as a provider in terms of whether a patient really benefits from it or needs it. Could there be a way to better assess a patient's risk for cancer coming back and apply an intervention like chemotherapy to the higher-risk patient and maybe not to the lower-risk patient? This strategy is already pretty common in breast cancer care and in colon cancer and prostate cancer care. And so this study employed a molecular classifier. It's a 14-gene expression assay from a company called Razor Genomics. This assay was already prospectively validated in over 1500 patients in two single-cohort trials close to 10 years ago. But this is a randomized trial we presented using that assay. And so here's how it went. Patients had non-squamous, non-small cell lung cancer. The assay was validated on non-squamous histology. Everybody had stage 1A, 1B, and 2A non-small cell lung cancer. Everybody had surgery, and then after surgery the tumor was assessed using this 14-gene classifier, and the results came back in about 10 days and you were scored as a low risk, intermediate, or high risk. If you had a low-risk score, you didn't need any additional intervention. We know from those earlier cohorts that there's over a 95% chance of being cured if you're a low-risk early-stage cancer. But if you were in the intermediate or high-risk score, you entered the study and you were randomized to 4 cycles of adjuvant platinum doublet chemotherapy—something we were routinely using in stage 2 and 3 disease—or to observation. The study was designed to look at an endpoint called disease-free survival, how long you live without cancer coming back. And so the study started and then was stopped early. The data safety monitoring board said there's already a dramatic result and this trial should stop early, and hence why we presented as a late breaker. So a little under 100 patients were in the experimental arm—that is, patients with intermediate or high-risk scores who received chemotherapy. And then a little over 100 patients were in the control arm when the trial was stopped. And the reason it was stopped was because of the overwhelming advantage in favor of the patients who got chemotherapy. So those patients that were intermediate and high risk who got chemo had an absolute advantage in terms of disease-free survival at 24 months. Specifically, the hazard ratio was 0.22. In other words, there was a 78% reduction in the risk of cancer coming back or dying if you'd gotten chemotherapy. And so that's where we're at. This assay is already available, and I think where we're at now is a patient walks into the clinic, has had surgery, has stage 1A, 1B, and even 2A non-small cell lung cancer. If you know that chemotherapy is what you recommend based on everything you know about the patient and they want that, this test is not for them. If you know you don't want to do it for whatever reason—you know chemo's not, maybe a patient comes into it saying they don't want it. No matter what you say, there are certain scenarios like that. This test is not for them either. But for those patients who are like, should I do more? I'm not sure. I have an early-stage cancer. I'm on the fence about chemo. This risk classifier can help patients be armed with information and their providers to say, hey, I have a low-risk cancer, I can feel pretty good about not doing anything more. Or I have an intermediate or high-risk cancer where chemotherapy could help dramatically—close to 80% improvement in my risk reduction for cancer returning or dying from cancer. And so I think this is a big step forward and certainly something doctors and patients and their families are going to want to use to help plan their treatment.