Chapters Transcript Video NSCLC Study Presented by Julia Rotow, MD. Dr. Julia Rotow presented results from a study using a cell-free DNA (cfDNA)-guided strategy to personalize first-line treatment for advanced non-small cell lung cancer. So in this study, we evaluated a plasma guided adaptive first-line treatment strategy for newly diagnosed metastatic non-small cell lung cancer. A significant unmet need in the field is to understand for patients with newly diagnosed lung cancer, who requires chemotherapy in the first line setting as a chemo immunotherapy regimen and who can have immunotherapy alone and do quite well and potentially have a durable response. In clinical practice, the most important biomarker to decide this has been PDL1 status for PDL one high patients tend to get immunotherapy, monotherapy. It's not a perfect biomarker. We know some people with high scores will have uh insufficient clinical response to therapy, and some with low PDL1 scores could do just fine with immunotherapy, monotherapy. And put off the potential toxicity and risk of, of upfront first on chemotherapy. So here we asked whether using a dynamic biomarker, in this case, plasma clearance or plasma reduction in tumor CTDNA uh detectable in the blood, could help us make a more informed choice between these two different regimens. So in this study, we took patients uh with first line PDL1 positive lung cancer who were enrolled on the study and treated them with a checkpoint inhibitor immunotherapy, monotherapy with pembrolizumab for two cycles. We checked their plasma levels pre-treatment and after the 1st 3 weeks, and then we also checked their imaging scans after those two rounds of treatment. And for those patients who had intermediate scan results, so stable scan findings or some disease progression which was was uh asymptomatic. We uh use the plasma levels to guide our treatment decision making, and those without a response were intensified with the addition of platinum doublet, and those who had a good plasma response to therapy could stay on immunotherapy alone. We follow patients long term for their outcomes on treatment with this adaptive strategy. What we found by doing this is that overall, we achieved response rates to about 50% and uh survival times of progression through survival of 11 months, that at least comparable to those seen in the prior historical data looking at combination chemo immunotherapy in all patients that newly diagnosed disease. However, half as many patients required upfront platinum doublet. As those who would have needed it in a predictive fashion based on historical standard of care strategies. So we believe that using these sorts of adaptive designs may allow us to spare some patients chemotherapy upfront, while still preserving a way to identify those patients who could do well on monotherapy. Now this is not a randomized study, so certainly further randomized confirmation of this, comparing the strategy to more standard PDL one guided strategies would be helpful to help understand how to integrate this into clinical practice in the long term, we think promising data and we hope will be helpful to our patients. Published June 11, 2025 Created by Related Presenters Julia Rotow, MD Medical Oncology View full profile