TP53 Co-Mutation Background and the TOP Study Design and Results

This opening segment introduces an OncLive program built around ASCO data on risk-guided treatment intensification and sequencing in EGFR-mutated advanced non-small cell lung cancer (NSCLC). TP53 co-mutations are a common negative prognostic marker, occurring in an estimated 45% to 65% of patients and associated with shorter progression-free survival. Current NCCN Category 1 preferred frontline options for EGFR exon 19 deletion or L858R mutations include osimertinib monotherapy, osimertinib plus platinum-based chemotherapy, and amivantamab plus lazertinib. The segment then turns to discussion of the TOP study, the first phase 3 trial to prospectively enroll patients based on a concurrent TP53 mutation, randomizing them to osimertinib plus chemotherapy versus osimertinib monotherapy.