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Multicenter Study
. 2025 Oct:83:104473.
doi: 10.1016/j.breast.2025.104473. Epub 2025 Apr 10.

Immune-related adverse events among patients with early-stage triple-negative breast cancer treated with pembrolizumab plus chemotherapy: real-world data from the Neo-Real/GBECAM 0123 study

Matheus de Oliveira Andrade  1 , Isabella Gonçalves Gutierres  2 , Monique Celeste Tavares  3 , Isadora Martins de Sousa  3 , Flávia Cavalcanti Balint  3 , Ana Carolina Marin Comini  3 , Mariana Carvalho Gouveia  4 , José Bines  5 , Fernanda Madasi  6 , Rafael Dal Ponte Ferreira  7 , Daniela Dornelles Rosa  8 , Candice Lima Santos  9 , Daniele Assad-Suzuki  10 , Zenaide Silva de Souza  11 , Júlio Antônio Pereira de Araújo  12 , Débora de Melo Gagliato  13 , Carlos Henrique Dos Anjos  14 , Bruna M Zucchetti  15 , Anezka Ferrari  16 , Mayana Lopes de Brito  17 , Renata Cangussu  18 , Maria Marcela Fernandes Monteiro  19 , Paulo M Hoff  20 , Maria Del Pilar Estevez-Diz  20 , Laura Testa  21 , Romualdo Barroso-Sousa  22 , Renata Colombo Bonadio  23
Affiliations
Multicenter Study

Immune-related adverse events among patients with early-stage triple-negative breast cancer treated with pembrolizumab plus chemotherapy: real-world data from the Neo-Real/GBECAM 0123 study

Matheus de Oliveira Andrade et al. Breast. 2025 Oct.

Abstract

Background: Pembrolizumab combined with neoadjuvant chemotherapy is the standard of care for stage II-III triple-negative breast cancer (TNBC) based on the KEYNOTE-522 trial. However, 13 % of patients experienced immune-related adverse events (irAEs) of grade ≥3 in the trial. This study aims to describe patterns of irAEs in a real-world scenario during treatment with pembrolizumab for early-stage TNBC.

Methods: Patients treated with neoadjuvant pembrolizumab plus chemotherapy across ten Brazilian cancer centers were evaluated in the Neo-Real/GBECAM0123 study. This analysis focuses on irAE evaluation, including time to onset, management, and association between irAEs and pathological complete response (pCR).

Results: A total of 368 patients were included. Overall, 31 % of patients (n = 114) presented with any grade irAEs. Most of irAEs (72.8 %) occurred during the neoadjuvant phase while 28.1 % happened during the adjuvant period. The most frequent irAEs were endocrine (12.8 % of the entire cohort), cutaneous (7.6 %) and gastrointestinal (7.1 %). A total of 50 patients (13.6 %) experienced grade ≥3 irAEs, predominantly gastrointestinal (32 %). 58 patients (56 %) needed corticosteroids. Immunotherapy rechallenge was possible in 53 % of the cases; permanent discontinuation of pembrolizumab was necessary for 16 %. No significant association was observed between irAEs and clinic-pathologic features nor pCR status.

Conclusions: In this real-world analysis, we observed a similar incidence of irAEs as reported in the KEYNOTE-522 trial. Most patients experienced resolution of their irAEs, but some required permanent discontinuation of pembrolizumab. Additionally, there were lasting dysfunctions, particularly endocrine, demanding lifelong support. Careful monitoring and management of these events are essential.

Keywords: Immune-related adverse events; Immunotherapy; Triple-negative breast cancer.

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Conflict of interest statement

Declaration of interest statement The Authors declare no Competing Non-Financial Interests but the following Competing Financial Interests: RCB: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Nestle Health Science, Addium, Gilead, MSD, BMS, AstraZeneca, Ache, Pfizer. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, MSD, Lilly. Institutional Research grant: Novartis, AstraZeneca. JB: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Lilly, Gilead, Pfizer, Novartis, MSD, Roche, Knight Pharmaceuticals. Financial support for educational programs and symposia: Roche, Daiichi-Sankyo. DDR: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Lilly, Libbs, Pfizer, Novartis, Roche, GSK, Sanofi, Amgen, Zodiac Pharma. Financial support for educational programs and symposia: Roche. DAS: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo. Financial support for educational programs and symposia: AstraZeneca. JAPA: Speaker fees and/or honoraria for consulting or advisory functions: Novartis, AstraZeneca, MSD, Lilly. DMG: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Teva, Roche, AstraZeneca, Pfizer, Lilly, Novartis. Financial support for educational programs and symposia: AstraZeneca, Libbs, Roche. Research grant: Novartis. BMZ: AstraZeneca, Daiichi-Sankyo, Eli Lilly, Gilead, Pfizer, Novartis, MSD, Roche, Addium. AF: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Novartis, Gilead, MSD, BMS, AstraZeneca, Pfizer. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, MSD, Novartis. CHA: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Gilead AstraZeneca, Novartis, MSD. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, MSD, Lilly, Rcohe, Novartis, Gilead, Medscape. RC: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daichii-Sankyo, Eli Lilly, Gilead, MSD, and GSK. MMFM: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Eli Lilly, Gilead, Adium, Novartis, MSD, and Roche. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, Gilead, Eli Lilly, Roche, MSD and Novartis. PMH: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo. MPED: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca. LT: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, MSD, AstraZeneca, Pfizer, Lilly, Novartis, Roche, Pfizer. Financial support for educational programs and symposia: AstraZeneca, Roche, Gilead, MSD. Institutional Research grant: Novartis. RBS: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Eli Lilly, Gilead, Libbs, Pfizer, Novartis, MSD, and Roche. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, Gilead, Eli Lilly, and MSD. Institutional Research grant: AstraZeneca, Daiichi-Sankyo. MCG: Speaker fees and/or honoraria for consulting or advisory functions: GSK, Novartis, Knight Therapeutics, MSD. MOA, IGG, IMS, FCB, ACMC, MCT, FM, RPF, CLS, and ZSS declare no conflict of interest.

Figures

Fig. 1
Fig. 1
A: Types of immune-related adverse events (all-grade) by system. B: Frequency of irAEs by phase of treatment (neoadjuvant or adjuvant).
Fig. 2
Fig. 2
A: Types of grade ≥3 immune-related adverse events (irAEs). B: Distribution of ≥G3 irAEs by system.
Fig. 3
Fig. 3
Median time to onset of the main immune-related adverse events associated with pembrolizumab.
Fig. 4
Fig. 4
Immune-related adverse events-free survival curve.
Fig. 5
Fig. 5
Relationship between immune-related adverse events (irAEs) and pathological complete response (pCR) rate.
See this image and copyright information in PMC

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