2796eP Seizure related 6 homolog (SEZ6) expression pattern and prognostic impact in a real-world cohort of patients with small cell lung cancer

ConcertAI/Caris Patient360TM RW datasets were used to assess transcriptomic and genomic data from patients with SCLC. Patients were stratified into treatment-naïve (TN) and post-first-line (1L) treatment groups. Expression of SEZ6 and other BMs was evaluated by comparing mRNA levels across the 2 treatment groups. Spearmen correlation was used to assess the correlation of SEZ6 expression with B7H3 and DLL3. Cox proportional hazard ratio (HR) analysis was performed to evaluate prognostic impact of SEZ6 expression on overall survival (OS).

Among 164 patients in this RW cohort, 127 were TN and 19 were post-1L. Expression of SEZ6, B7H3, and DLL3 was similar between groups. There was no correlation between SEZ6 and B7H3 (0.027, P=0.735) and moderate correlation between SEZ6 and DLL3 expression (0.397, P=1.42E-07). SEZ6 expression lacked statistical significance as a prognostic BM for OS in all patients (HR=1.001 [0.998–1.005]; P=0.498). SCLC subtypes (A [ASCL1], N [NEUROD1], I [Inflamed], P [POU2F3]) distribution among TN patients (A=47.2%, N=38.6%, I and P=14.2%) was similar to that of post-1L patients (A=52.6%, N=31.6%, I and P=15.8%). SEZ6 expression was higher in subtypes A and N.

In this RW SCLC patient cohort, while SEZ6 expression was similar between TN and post-1L patients, it was not a prognostic BM. Expression of SEZ6 by mRNA correlates with that of DLL3 but lacks correlation with that of B7H3. SCLC subtypes (A, N, I, P) distribution is similar between TN and post-1L patients.