The following is a summary of “RELAY, Ramucirumab Plus Erlotinib (RAM+ERL) in Untreated Metastatic EGFR-Mutant NSCLC (EGFR+ NSCLC): Association Between TP53 Status and Clinical Outcome,” published in the July 2023 issue of the Clinical Lung Cancer by Nishio et al.
In RELAY, a randomized Phase III trial of patients with untreated, metastatic, EGFR-mutated, non-small-cell lung cancer (EGFR+ NSCLC), ramucirumab plus erlotinib (RAM+ERL) demonstrated superior progression-free survival (PFS). Here, researchers present the association between TP53 status and RELAY outcomes. Patients were administered ERL orally with intravenous RAM (10 mg/kg IV) or a placebo (PBO+ERL) every two weeks. Plasma was evaluated by Guardant 360 next-generation sequencing, and patients with any baseline gene mutation were included in this exploratory study.
Endpoints included progression-free survival, overall response rate, disease control rate, duration of response, overall survival, safety, and biomarker analysis. The relationship between TP53 status and outcomes was investigated. Mutant TP53 was detected in 165 (42.7%) patients (74 RAM+ERL, 91 PBO+ERL), while wild-type TP53 was detected in 221 (57.3%) patients (118 RAM+ERL, 103 PBO+ERL). Those with mutant and wild-type TP53 had comparable patient and disease characteristics and concurrent gene alterations. TP53 mutations, particularly in exon 8, were associated with worse clinical outcomes regardless of treatment. In every patient, RAM+ERL enhanced PFS.
While ORR and DCR were comparable across all patients, RAM+ERL produced a superior DoR. No clinically significant differences existed between those with baseline TP53 mutations and those with wild-type TP53. TP53 mutations are a negative prognostic indicator in EGFR+ NSCLC, but adding a VEGF inhibitor enhances the prognosis for those with TP53 mutations. Regardless of TP53 status, RAM+ERL is an effective first-line treatment option for patients with EGFR+ NSCLC.