International real-world study of DLL3 expression in patients with small cell lung cancer. (September 2020)

• Record Type: Journal Article
• Authors: Rojo, Federico; Corassa, Marcelo; Mavroudis, Dimitrios; Öz, Aysim Büge; Biesma, Bonne; Brcic, Luka; Pauwels, Patrick; Sailer, Verena; Gosney, John; Miljkovic, Darko; Hader, Carlos; Wu, Meijing; Almarez, Todd; Penault-Llorca, Frédérique
• Is Part Of: Lung cancer. Volume 147(2020)
• Page Start: 237
• Page End: 243
• Publication Date: 2020-09
• Subjects: DLL3 delta-like ligand 3 -- ECOG Eastern Cooperative Oncology Group -- FFPE formalin-fixed paraffin embedded -- IHC immunohistochemistry -- IQR interquartile range -- SCLC small cell lung cancer; Small cell lung cancer -- DLL3 -- Biomarker -- Real-world analysis; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2020.07.026
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: This is the largest epidemiologic study to evaluate DLL3 prevalence in SCLC. DLL3 was robustly expressed in SCLC across disease stages and lines of therapy. DLL3 expression remained stable over time despite treatment. There was no prognostic role for DLL3 in this study for overall survival. Median overall survival in SCLC is short, and new treatments are urgently needed. Abstract: Objectives: Expression of the Notch-family ligand delta-like protein 3 (DLL3), a potential therapeutic target in small cell lung cancer (SCLC), has not been assessed in the real-world setting. To identify the real-world utility of DLL3 as an SCLC therapeutic target, we performed the largest retrospective international noninterventional study to date to evaluate DLL3 prevalence in SCLC patients. Materials and Methods: DLL3 expression was assessed using immunohistochemistry in archived histological and cytological specimens (independent and paired) and correlated to patient demographics, clinical disease characteristics, and survival. The primary endpoint was the proportion of patients with DLL3 expression in ≥25 % of tumor cells. DLL3 expression concordance was assessed in paired specimens. Results: Independent tumor specimens were collected from 1073 patients. The mean age at biopsy was 66 years (SD, 10); 682 (64 %) patients were male. Paired specimens were collected from 36 patients. The mean age at biopsy was 62 years (SD, 11); 16 (44 %) patients were male. Most patients had ECOG performance status of 0–1, were smokers/ex-smokers, and received ≥1 prior therapy. Positive DLL3 expression (defined as ≥25 % of tumor cells) was identified in 895/1050 (85 %) patients with 1 specimen and evaluable DLL3 expression; 719/1050 (68 %) patients had high DLL3 expression (defined as ≥75 % of tumor cells). DLL3 expression concordance was 88 % between paired specimens (n = 17; Cohen's kappa P value, .9412). There was no significant difference in median overall survival from SCLC diagnosis for evaluable patients with nonmissing data based on DLL3 expression (negative DLL3 expression [n = 139], 9.5 months; positive DLL3 expression [n = 747], 9.5 months; all evaluable patients [n = 893, 9.5 months). Conclusion: These real-world epidemiologic findings indicate that DLL3 is robustly expressed across SCLC disease stages and remains stable despite treatment, consistent with available clinical trial data. There was no prognostic role for DLL3 observed in this study for overall survival.