ESMO 2025 | Systemic therapy options for patients with NSCLC who relapse

So in early and locally advanced response to lung cancer, all our active agents that have transformed the face of stage four lung cancer are now being used in 1B stage two or stage three lung cancer. So for the EGFR and ALK negative group, we’re generally using immunotherapy either before surgery, before and after surgery, or only after surgery. And for stage three inoperable, they’re getting immunotherapy after chemoradiation. Now, what do we do when those patients relapse? It’s difficult to know whether the patient’s tumor still is immune sensitive or not. Now, of course, in England, we have access issues to using checkpoint inhibitors after relapse. So we have to bear in mind our decision making in the context of access to checkpoint inhibitors. But in general, the principles are that if a patient progresses during checkpoint inhibitor therapy, they probably have acquired checkpoint inhibitor resistance. And in that setting, I’m not sure that we want to be carrying on a checkpoint inhibitor in combination with chemotherapy. We need to be thinking about the second line setting for those patients. And there may be a group of patients with a long platinum-free interval that we might want to be re-challenging with platinum doublet in that setting with a view to then subsequent treatment thereafter. Things get more complex in the EGFR-ALK-positive space because these patients are getting adjuvant osimertinib in the ADURA indication or adjuvant alectinib in the ALINA population. We know that a proportion of these patients are highly sensitive to these drugs, and these drugs probably are not curing patients, but just pushing back the time until relapse. So if patients progress on these TKIs, they probably have acquired resistance, and we should be managing them like acquired resistance in the stage four setting. If they progress when they’ve discontinued their drugs because they’ve reached the end of their two years or three years of therapy, then that may be because they’re still dependent on that and re-challenge is really important to that group of patients. So this area is getting very complex, getting very difficult to interpret, and understanding the kinetics of relapse, understanding the sites of relapse, understanding the intrinsic sensitivity and dependence of drugs that these patients have is really critical to optimal decision making.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.