Utilizing TP53 mutation status and initial disease burden at presentation to risk-stratify patients with advanced EGFR-mutated NSCLC treated with osimertinib.

Abstract

e20663 Background: There are multiple FDA approved first line options for stage IV EGFR mutated NSCLC but no clear prognostic models to guide treatment. This study aimed to investigate how two known risk factors in EGFR mutated NSCLC, (1) TP53 mutations and (2) high burden of disease (defined as 2 or more extrathoracic metastases), individually and additively impacted outcomes of first line osimertinib monotherapy. Methods: Patients with stage IV NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations per OHSU Genetrails molecular panel from 2018-2024 were screened. Relevant demographic and clinical information were collected via chart review. Patients were included for analysis if they received first-line osimertinib therapy with reliable documentation of progression and survival. Survival analyses were conducted using Kaplan-Meier methods and univariable Cox Proportional Hazards regression, with log-log confidence intervals for hazard ratio estimates. Results: 34 patients met inclusion criteria; baseline characteristics at osimertinib start are shown in Table 1. High burden of disease (n=21) was associated with significantly lower median progression-free survival (PFS) than low burden of disease (n=13); 13.5 vs 20.6 months, p = 0.008. This was not associated with a significant difference in overall survival (OS). TP53 mutations (n=21) were not associated with a significant PFS or OS difference compared with TP53 wildtype (n=13). Having both TP53 mutations and high burden of disease (n=14) was not associated with inferior outcomes compared with having either 0 (n=6) or 1 (n=14) risk factors. Neither ECOG PS nor specific EGFR mutation (exon 19 del vs L858R) were associated with significant OS or PFS differences. Conclusions: In patients with stage IV EGFR mutated NSCLC treated with 1L osimertinib, baseline high burden of disease was associated with lower PFS but not OS, while TP53 mutations were not associated with differences in outcome. To our knowledge, this is the first study in this population using a single dataset with reliable clinical data aiming to portray the individual and combined impact of clinical and molecular risk factors. Disease burden merits further exploration as a stratifying factor in studies of treatment optimization for advanced EGFR mutated NSCLC. Baseline characteristics. Characteristic Overall (N=34) Low disease burden (N=13) High disease burden (N=21) Male sex: n (%) 9 (26.5%) 3 (23.1%) 6 (28.6%) Age: mean (SD) 64.0 (9.43) 64.2 (11.3) 63.9 (8.36) TP53 mutated: n (%) 21 (61.8%) 7 (53.8%) 14 (66.7%) Exon 19 deletion: n (%) 21 (61.8%) 9 (69.2%) 12 (57.1%) Exon 21 L858R: n (%) 13 (38.2%) 4 (30.8%) 9 (42.9%) ECOG PS 0: n (%) 13 (38.2%) 7 (53.8%) 6 (28.6%) ECOG PS 1: n (%) 6 (17.6%) 1 (7.7%) 5 (23.8%) ECOG PS 2: n (%) 6 (17.6%) 1 (7.7%) 5 (23.8%) ECOG PS missing: n (%) 9 (26.5%) 4 (30.8%) 5 (23.8%)