TOP Trial: Chemo-Osimertinib in TP53-Mutant EGFR-Mutated NSCLC

The TOP trial, a phase three study focused exclusively on TP53-mutant EGFR-mutant non-small cell lung cancer, validated the FLAURA2 findings in this high-risk subset, showing a striking PFS benefit of 34.0 versus 15.6 months (HR 0.44) for osimertinib plus chemotherapy over monotherapy, with a favorable duration of response of 32.7 versus 15.9 months, though overall survival data remain immature. Debate arose around the ethics of randomizing known high-risk patients to monotherapy, with panelists suggesting future trials should instead focus on de-escalation in low-risk patients lacking TP53, CNS disease, or elevated ctDNA. Discussion also highlighted ongoing efforts to use ctDNA clearance as a biomarker to guide chemotherapy addition adaptively, and the potential role of local therapies for oligometastatic disease as an alternative to systemic intensification.