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

ABSTRACT

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.

KEYWORDS:

• Early triple negative breast cancer
• checkpoint inhibition
• neoadjuvant
• pembrolizumab

Disclosure statement

TR has received financial contributions to attend meetings from Daiichi Sankyo, Amgen, and MSD. MM has received honoraria for lectures, advisory board participation and consultation from Roche, Eli Lilly, Novartis, Astra Zeneca, Daiichi Sankyo, Pfizer, MSD, Gilead, and Medmedia, and travel support from Amgen, Gilead, Roche, Novartis, Pierre Fabre, Daiichi Sankyo, and Eisai.

Author contributions

MM, RB and TR designed the study and its methodology. Data collection was performed by SU, AH, MH, MF, KW, ZBH, RE, FF and KSW. Data input was performed by MM, SU, and AH. Data analysis as well as creation of figures and tables was performed by MM and SU. MM and RB wrote the manuscript. All authors read and approved the manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2275846

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.