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

Autor: Rojo F; Hospital Universitario Fundación Jiménez Díaz CIBERONC, Madrid, Spain. Electronic address: frojo@fjd.es., Corassa M; A.C. Camargo Cancer Center, São Paulo, Brazil., Mavroudis D; University General Hospital of Heraklion, Heraklion, Greece., Öz AB; Istanbul University Cerrahpaşa, Faculty of Medicine, Istanbul, Turkey., Biesma B; Jeroen Bosch Ziekenhuis,' s-Hertogenbosch, Netherlands., Brcic L; Medical University of Graz, Graz, Austria., Pauwels P; Centre for Oncological Research (CORE), University of Antwerp, and University Hospital Antwerp, Edegem, Belgium., Sailer V; University Hospital Schleswig-Holstein, Lübeck, Germany., Gosney J; Liverpool University Hospitals, Liverpool, United Kingdom., Miljkovic D; AbbVie Inc., North Chicago, IL, United States., Hader C; AbbVie Inc., North Chicago, IL, United States., Wu M; AbbVie Inc., North Chicago, IL, United States., Almarez T; AbbVie Inc., North Chicago, IL, United States., Penault-Llorca F; University Clermont Auvergne, Jean Perrin Center, INSERM, IMoST, 63000 Clermont-Ferrand, France.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2020 Sep; Vol. 147, pp. 237-243. Date of Electronic Publication: 2020 Jul 27.
DOI: 10.1016/j.lungcan.2020.07.026
Abstrakt: 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.
(Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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