Immune-related adverse events with (neo)adjuvant pembrolizumab in patients with early-stage triple-negative breast cancer

Background: Pembrolizumab (P) combined with neoadjuvant chemotherapy (CT) is the standard of care for stage II-III triple-negative breast cancer (TNBC) based on the Keynote-522 trial. However, approximately 13% of patients (pts) experience immune-related adverse events (irAEs) of grade ≥3.

Objective: This study aims to describe patterns of irAEs in real-world scenarios during P treatment for early-stage TNBC.

Methods: The Neo-Real/GBECAM 0123 study is a real-world collaborative study evaluating pts with early-stage TNBC treated with neoadjuvant P plus CT between July 2020 and July 2024 across ten Brazilian cancer centers. This analysis focuses on irAE evaluation, including time to onset, management, resolution, and the association between irAEs and pathological complete response (pCR).

Results: A total of 368 pts were included, with a median age of 43 years (range 23-87); 70.9% had stage II and 25.5% had stage III disease. Overall, 31% of patients (n = 114) presented with any grade of irAEs. Most of irAEs (73%) occurred during the neoadjuvant phase while 27% happened during the adjuvant period. The most frequent irAEs were endocrine (34.3%), cutaneous (20.4%) and gastrointestinal (19%). A total of 45 pts (12%) experienced grade ≥3 irAEs, predominantly gastrointestinal (34%), with a 22.6% incidence of hepatitis. No fatal irAEs occurred. The median duration of irAEs was 29.5 days (range 2-418). Among the 114 who presented with irAEs, 58 pts (53.6%) needed corticosteroids, and 2 pts required additional immunosuppressive therapy. At last follow-up, 69.9% of irAEs had resolved. Among 31 pts with persistent irAEs, most had endocrine irAE: thyroiditis (17), adrenal insufficiency (4), hypophysitis (2), and diabetes mellitus (1). Immunotherapy rechallenge was possible in 53.6% of cases. Permanent discontinuation of P was necessary for 51 pts (13.9% of those exposed to P). No significant association was observed between irAEs and clinic-pathologic features nor pCR status.

Conclusions: In this real-world data analysis, we observed a similar incidence of irAEs as reported in the Keynote-522 trial. Most pts experienced resolution of their irAEs, but a significant proportion required permanent discontinuation of pembrolizumab. Additionally, some pts experienced lasting dysfunctions, particularly endocrine, demanding lifelong support. Careful monitoring and management of these events are essential. Identifying pts who do not require pembrolizumab remains a challenge.

Corresponding author: Isabella Gonçalves Gutierres (e-mail: isabellagguti@gmail.com).