Real-world clinical outcomes among patients with EGFR-mutated (Ex19del/L858R) metastatic NSCLC treated at City of Hope with osimertinib monotherapy by TP53 alteration status.

Abstract

703 Background: Epidermal growth factor receptor mutations (EGFRm) occur in ~15% of non-small cell lung cancer (NSCLC) cases, with exon 19 deletions (Ex19del) and exon 21 L858R substitutions (L858R) comprising 85-90%. Osimertinib (Osi) monotherapy (mono) is one of the first-line (1L) treatment options, while more effective combination regimens have recently become available. TP53 co-alterations occur in ~50% of EGFRm NSCLC and have been associated with inferior outcomes with Osi, warranting further real-world study. This study describes clinical outcomes of patients with EGFRm (Ex19del/L858R) metastatic NSCLC receiving Osi mono as their first treatment at City of Hope, stratified by TP53 alteration status. Methods: Adults with EGFRm (Ex19del/L858R) metastatic NSCLC initiating Osi mono as their first observed treatment were descriptively analyzed using City of Hope’s electronic medical records (1/1/2018–12/31/2025). Biomarker status was assessed pre-Osi. Time to discontinuation (TTD), time to next treatment (TTNT), and overall survival (OS) from Osi initiation were assessed using Kaplan-Meier analysis. Results: Among 108 patients initiating Osi mono as their first treatment, median age was 65.5 years, 63.9% were female, and 55.6% were Asian; median follow-up was 27.5 months. Overall, 94.4% (n=102) discontinued Osi, primarily due to progression (70.6%; n=72) with median TTD, TTNT, and OS of 15.1, 16.1, and 29.1 months, respectively (Table). Of 59 patients (54.6%) with co-alteration testing pre-Osi, TP53 alterations (of any type) were detected in 66.1% (n=39). Patients with TP53 alterations had similar median TTD and TTNT relative to those without TP53 alterations (n=69), but descriptively shorter median OS (26.2; 30.4 months), and numerically higher rates of discontinuation due to progression (76.3%; 67.2%) and death (7.9%; 4.7%), respectively. Conclusions: Among patients with EGFRm (Ex19del/L858R) metastatic NSCLC receiving Osi mono as their first observed treatment, those with TP53 alterations had numerically higher discontinuation due to progression or death, and shorter OS, suggesting a need for more durable and effective therapies in this subgroup. Median TTNT and TTD were consistent with other real-world studies. Future analyses with more recent data of emerging 1L combination regimens are needed. Osi mono N = 108 TP53-alteredN = 39 Non-TP53-alteredN = 69 Follow-up (months), mean [median] 31.2 [27.5] 28.9 [25.8] 32.6 [28.4] Age (years), mean [median] 64.2 [65.5] 66.8 [68.0] 62.7 [63.0] Patients discontinuing Osi, n (%) 102 (94.4) 38 (97.4) 64 (92.8) Progression 72 (70.6) 29 (76.3) 43 (67.2) Death 6 (5.9) 3 (7.9) 3 (4.7) Median TTD (months) 15.1 14.6 15.3 Median TTNT (months) 16.1 16.8 15.9 Treatment-free interval (months), mean ± standard deviation 0.7 ± 2.6 0.8 ± 3.5 0.6 ± 1.8 Median OS (months) 29.1 26.2 30.4