Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer

Based upon results of the KEYNOTE-522 trial and following approval by regulatory authorities, the addition of pembrolizumab to chemotherapy is now the standard-of-care for the treatment of early triple-negative breast cancer (eTNBC) (Clinical stage II-III). Pembrolizumab is a programmed cell death p...

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Main Authors: Maximilian Marhold, Simon Udovica, Anna Halstead, Mona Hirdler, Muna Ferner, Kerstin Wimmer, Zsuzsanna Bago-Horvath, Ruth Exner, Florian Fitzal, Kathrin Strasser-Weippl, Tim Robinson, Rupert Bartsch
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:OncoImmunology
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Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2023.2275846
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author Maximilian Marhold
Simon Udovica
Anna Halstead
Mona Hirdler
Muna Ferner
Kerstin Wimmer
Zsuzsanna Bago-Horvath
Ruth Exner
Florian Fitzal
Kathrin Strasser-Weippl
Tim Robinson
Rupert Bartsch
author_facet Maximilian Marhold
Simon Udovica
Anna Halstead
Mona Hirdler
Muna Ferner
Kerstin Wimmer
Zsuzsanna Bago-Horvath
Ruth Exner
Florian Fitzal
Kathrin Strasser-Weippl
Tim Robinson
Rupert Bartsch
author_sort Maximilian Marhold
collection DOAJ
description Based upon results of the KEYNOTE-522 trial and following approval by regulatory authorities, the addition of pembrolizumab to chemotherapy is now the standard-of-care for the treatment of early triple-negative breast cancer (eTNBC) (Clinical stage II-III). Pembrolizumab is a programmed cell death protein 1 monoclonal antibody, known to cause immune-related adverse events (irAEs) in a significant subset of patients. Real-world data on incidence, type and treatment strategies of irAEs in the setting of eTNBC treatment are sparse. In this multicenterretrospective analysis, we characterized real-world incidence of irAEs and treatment outcomes such as pathological complete response (pCR) from the combination of pembrolizumab and chemotherapy as neoadjuvant treatment for eTNBC.We found a rate of irAEs of all grades of 63.9% and of 20% for irAEs of grade 3 or higher. In the overall population, a pCR rate of 57.1% was observed. The emergence of irAEs correlated significantly with pCR (72.2% versus 30.8%; p =.03). Discontinuation of neoadjuvant chemotherapy before week 12 correlated significantly with a lower pCR rate.To our knowledge, this is the first study evaluating the real-world efficacy and safety of a neoadjuvant combination of chemotherapy and pembrolizumab in eTNBC, demonstrating a significant correlation between irAEs and pCR. Early discontinuation of neoadjuvant therapy due to AEs resulted in a lower pCR rate.
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spelling doaj-art-1ff23e6d3c4f4d5ba552842c9e055d6a2025-08-20T02:50:44ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2275846Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancerMaximilian Marhold0Simon Udovica1Anna Halstead2Mona Hirdler3Muna Ferner4Kerstin Wimmer5Zsuzsanna Bago-Horvath6Ruth Exner7Florian Fitzal8Kathrin Strasser-Weippl9Tim Robinson10Rupert Bartsch11Division of Oncology, Department for Medicine I, Medical University of Vienna, Vienna, AustriaDepartment of Medicine I, Center for Oncology and Hematology, Clinic Ottakring, Vienna, AustriaBristol Medical School, University of Bristol, Bristol, UKDepartment of Internal Medicine I for Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, Linz, AustriaDepartment of Medicine I, Center for Oncology and Hematology, Clinic Ottakring, Vienna, AustriaDepartment of General Surgery, Medical University of Vienna, Vienna, AustriaInstitute for Pathology, Medical University of Vienna, Vienna, AustriaDepartment of General Surgery, Medical University of Vienna, Vienna, AustriaDepartment of General Surgery, Medical University of Vienna, Vienna, AustriaDepartment of Medicine I, Center for Oncology and Hematology, Clinic Ottakring, Vienna, AustriaBristol Medical School, University of Bristol, Bristol, UKDivision of Oncology, Department for Medicine I, Medical University of Vienna, Vienna, AustriaBased upon results of the KEYNOTE-522 trial and following approval by regulatory authorities, the addition of pembrolizumab to chemotherapy is now the standard-of-care for the treatment of early triple-negative breast cancer (eTNBC) (Clinical stage II-III). Pembrolizumab is a programmed cell death protein 1 monoclonal antibody, known to cause immune-related adverse events (irAEs) in a significant subset of patients. Real-world data on incidence, type and treatment strategies of irAEs in the setting of eTNBC treatment are sparse. In this multicenterretrospective analysis, we characterized real-world incidence of irAEs and treatment outcomes such as pathological complete response (pCR) from the combination of pembrolizumab and chemotherapy as neoadjuvant treatment for eTNBC.We found a rate of irAEs of all grades of 63.9% and of 20% for irAEs of grade 3 or higher. In the overall population, a pCR rate of 57.1% was observed. The emergence of irAEs correlated significantly with pCR (72.2% versus 30.8%; p =.03). Discontinuation of neoadjuvant chemotherapy before week 12 correlated significantly with a lower pCR rate.To our knowledge, this is the first study evaluating the real-world efficacy and safety of a neoadjuvant combination of chemotherapy and pembrolizumab in eTNBC, demonstrating a significant correlation between irAEs and pCR. Early discontinuation of neoadjuvant therapy due to AEs resulted in a lower pCR rate.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2275846Early triple negative breast cancercheckpoint inhibitionneoadjuvantpembrolizumab
spellingShingle Maximilian Marhold
Simon Udovica
Anna Halstead
Mona Hirdler
Muna Ferner
Kerstin Wimmer
Zsuzsanna Bago-Horvath
Ruth Exner
Florian Fitzal
Kathrin Strasser-Weippl
Tim Robinson
Rupert Bartsch
Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer
OncoImmunology
Early triple negative breast cancer
checkpoint inhibition
neoadjuvant
pembrolizumab
title Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer
title_full Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer
title_fullStr Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer
title_full_unstemmed Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer
title_short Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer
title_sort emergence of immune related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple negative breast cancer
topic Early triple negative breast cancer
checkpoint inhibition
neoadjuvant
pembrolizumab
url https://www.tandfonline.com/doi/10.1080/2162402X.2023.2275846
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