RELAY, Ramucirumab Plus Erlotinib (RAM plus ERL) in Untreated Metastatic EGFR-Mutant NSCLC (EGFR plus NSCLC) : Association Between TP53 Status and Clinical Outcome

Mutant TP53 is a negative prognostic factor in patients with EGFR +NSCLC. This exploratory analysis inves-tigated the association between TP53 status and clinical outcome in RELAY. The findings indicated that RAM +ERL exhibited benefit compared with PBO +ERL, independent of TP53 status. The RELAY regimen is an efficacious first-line treatment option for all patients with EGFR +NSCLC, with or without TP53 mutation. Background: Ramucirumab plus erlotinib (RAM + ERL) demonstrated superior progression-free survival (PFS) in RELAY, a randomised Phase III trial in patients with untreated, metastatic, EGFR-mutated, non-small-cell lung cancer (EGFR+ NSCLC). Here, we present the relationship between TP53 status and outcomes in RELAY. Materials and Methods: Patients received oral ERL plus intravenous RAM (10 mg/kg IV) or placebo (PBO + ERL) every 2 weeks. Plasma was assessed by Guardant 360 next-generation sequencing and patients with any gene alteration detected at baseline were included in this exploratory analysis. Endpoints included PFS, overall response rate (ORR), disease control rate (DCR), DoR, overall survival (OS), safety, and biomarker analysis. The association between TP53 status and outcomes was evaluated. Results: Mutated TP53 was detected in 165 (42.7%; 74 RAM + ERL, 91 PBO + ERL) patients, wild-type TP53 in 221 (57.3%; 118 RAM + ERL, 103 PBO + ERL) patients. Patient and disease characteristics and concurrent gene alterations were comparable between those with mutant and wildtype TP53. Independent of treat-ment, TP53 mutations, most notably on exon 8, were associated with worse clinical outcomes. In all patients, RAM + ERL improved PFS. While ORR and DCR were comparable across all patients, DoR was superior with RAM + ERL. There were no clinically meaningful differences in the safety profiles between those with baseline TP53 mutation and wild-type. Conclusion: This analysis indicates that while TP53 mutations are a negative prognostic marker in EGFR+ NSCLC, the addition of a VEGF inhibitor improves outcomes in those with mutant TP53. RAM + ERL is an efficacious first-line treatment option for patients with EGFR+ NSCLC, independent of TP53 status.