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Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples

Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate directed against Delta-like protein 3 (DLL3), is under development for patients with small cell lung cancer (SCLC). DLL3 is expressed on the majority of SCLC samples. Because SCLC is rarely biopsied in the course of disease, data regarding...

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Autores principales: Kuempers, Christiane, Jagomast, Tobias, Krupar, Rosemarie, Paulsen, Finn-Ole, Heidel, Carsten, Ribbat-Idel, Julika, Idel, Christian, Märkl, Bruno, Anlauf, Martin, Berezowska, Sabina, Tiemann, Markus, Bösmüller, Hans, Fend, Falko, Kalsdorf, Barbara, Bohnet, Sabine, Dreyer, Eva, Sailer, Verena, Kirfel, Jutta, Perner, Sven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531433/
https://www.ncbi.nlm.nih.gov/pubmed/34692726
http://dx.doi.org/10.3389/fmed.2021.734901
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author Kuempers, Christiane
Jagomast, Tobias
Krupar, Rosemarie
Paulsen, Finn-Ole
Heidel, Carsten
Ribbat-Idel, Julika
Idel, Christian
Märkl, Bruno
Anlauf, Martin
Berezowska, Sabina
Tiemann, Markus
Bösmüller, Hans
Fend, Falko
Kalsdorf, Barbara
Bohnet, Sabine
Dreyer, Eva
Sailer, Verena
Kirfel, Jutta
Perner, Sven
author_facet Kuempers, Christiane
Jagomast, Tobias
Krupar, Rosemarie
Paulsen, Finn-Ole
Heidel, Carsten
Ribbat-Idel, Julika
Idel, Christian
Märkl, Bruno
Anlauf, Martin
Berezowska, Sabina
Tiemann, Markus
Bösmüller, Hans
Fend, Falko
Kalsdorf, Barbara
Bohnet, Sabine
Dreyer, Eva
Sailer, Verena
Kirfel, Jutta
Perner, Sven
author_sort Kuempers, Christiane
collection PubMed
description Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate directed against Delta-like protein 3 (DLL3), is under development for patients with small cell lung cancer (SCLC). DLL3 is expressed on the majority of SCLC samples. Because SCLC is rarely biopsied in the course of disease, data regarding DLL3 expression in relapses is not available. The aim of this study was to investigate the expression of DLL3 in chemorelapsed (but untreated with Rova-T) SCLC samples and compare the results with chemonaive counterparts. Two evaluation methods to assess DLL3 expression were explored. Additionally, we assessed if DLL3 expression of chemorelapsed and/or chemonaive samples has prognostic impact and if it correlates with other clinicopathological data. The study included 30 paired SCLC samples, which were stained with an anti DLL3 antibody. DLL3 expression was assessed using tumor proportion score (TPS) and H-score and was categorized as DLL3 low (TPS < 50%, H-score ≤ 150) and DLL3 high (TPS ≥ 50%, H-score > 150). Expression data were correlated with clinicopathological characteristics. Kaplan–Meier curves were used to illustrate overall survival (OS) depending on DLL3 expression in chemonaive and chemorelapsed samples, respectively, and depending on dynamics of expression during course of therapy. DLL3 was expressed in 86.6% chemonaive and 80% chemorelapsed SCLC samples without significant differences between the two groups. However, the extent of expression varied in a substantial proportion of pairs (36.6% with TPS, 43.3% with H-score), defined as a shift from low to high or high to low expression. TPS and H-score provided comparable results. There were no profound correlations with clinicopathological data. Survival analysis revealed a trend toward a more favorable OS in DLL low-expressing chemonaive SCLC (p = 0.57) and, in turn, in DLL3 high-expressing chemorelapsed SCLC (p = 0.42) as well as in SCLC demonstrating a shift from low to high expression (p = 0.56) without being statistically significant. This is the first study to investigate DLL3 expression in a large cohort of rare paired chemonaive-chemorelapsed SCLC specimens. Comparative analysis revealed that DLL3 expression was not stable during the course of therapy, suggesting therapy-based alterations. Unlike in chemonaive samples, a high DLL3 expression in chemorelapsed samples indicated a trend for a more favorable prognosis. Our results highlight the importance to investigate DLL3 in latest chemorelapsed SCLC tumor tissue.
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spelling pubmed-85314332021-10-23 Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples Kuempers, Christiane Jagomast, Tobias Krupar, Rosemarie Paulsen, Finn-Ole Heidel, Carsten Ribbat-Idel, Julika Idel, Christian Märkl, Bruno Anlauf, Martin Berezowska, Sabina Tiemann, Markus Bösmüller, Hans Fend, Falko Kalsdorf, Barbara Bohnet, Sabine Dreyer, Eva Sailer, Verena Kirfel, Jutta Perner, Sven Front Med (Lausanne) Medicine Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate directed against Delta-like protein 3 (DLL3), is under development for patients with small cell lung cancer (SCLC). DLL3 is expressed on the majority of SCLC samples. Because SCLC is rarely biopsied in the course of disease, data regarding DLL3 expression in relapses is not available. The aim of this study was to investigate the expression of DLL3 in chemorelapsed (but untreated with Rova-T) SCLC samples and compare the results with chemonaive counterparts. Two evaluation methods to assess DLL3 expression were explored. Additionally, we assessed if DLL3 expression of chemorelapsed and/or chemonaive samples has prognostic impact and if it correlates with other clinicopathological data. The study included 30 paired SCLC samples, which were stained with an anti DLL3 antibody. DLL3 expression was assessed using tumor proportion score (TPS) and H-score and was categorized as DLL3 low (TPS < 50%, H-score ≤ 150) and DLL3 high (TPS ≥ 50%, H-score > 150). Expression data were correlated with clinicopathological characteristics. Kaplan–Meier curves were used to illustrate overall survival (OS) depending on DLL3 expression in chemonaive and chemorelapsed samples, respectively, and depending on dynamics of expression during course of therapy. DLL3 was expressed in 86.6% chemonaive and 80% chemorelapsed SCLC samples without significant differences between the two groups. However, the extent of expression varied in a substantial proportion of pairs (36.6% with TPS, 43.3% with H-score), defined as a shift from low to high or high to low expression. TPS and H-score provided comparable results. There were no profound correlations with clinicopathological data. Survival analysis revealed a trend toward a more favorable OS in DLL low-expressing chemonaive SCLC (p = 0.57) and, in turn, in DLL3 high-expressing chemorelapsed SCLC (p = 0.42) as well as in SCLC demonstrating a shift from low to high expression (p = 0.56) without being statistically significant. This is the first study to investigate DLL3 expression in a large cohort of rare paired chemonaive-chemorelapsed SCLC specimens. Comparative analysis revealed that DLL3 expression was not stable during the course of therapy, suggesting therapy-based alterations. Unlike in chemonaive samples, a high DLL3 expression in chemorelapsed samples indicated a trend for a more favorable prognosis. Our results highlight the importance to investigate DLL3 in latest chemorelapsed SCLC tumor tissue. Frontiers Media S.A. 2021-10-08 /pmc/articles/PMC8531433/ /pubmed/34692726 http://dx.doi.org/10.3389/fmed.2021.734901 Text en Copyright © 2021 Kuempers, Jagomast, Krupar, Paulsen, Heidel, Ribbat-Idel, Idel, Märkl, Anlauf, Berezowska, Tiemann, Bösmüller, Fend, Kalsdorf, Bohnet, Dreyer, Sailer, Kirfel and Perner. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Kuempers, Christiane
Jagomast, Tobias
Krupar, Rosemarie
Paulsen, Finn-Ole
Heidel, Carsten
Ribbat-Idel, Julika
Idel, Christian
Märkl, Bruno
Anlauf, Martin
Berezowska, Sabina
Tiemann, Markus
Bösmüller, Hans
Fend, Falko
Kalsdorf, Barbara
Bohnet, Sabine
Dreyer, Eva
Sailer, Verena
Kirfel, Jutta
Perner, Sven
Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples
title Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples
title_full Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples
title_fullStr Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples
title_full_unstemmed Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples
title_short Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples
title_sort delta-like protein 3 expression in paired chemonaive and chemorelapsed small cell lung cancer samples
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531433/
https://www.ncbi.nlm.nih.gov/pubmed/34692726
http://dx.doi.org/10.3389/fmed.2021.734901
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