Treatment outcomes with pembrolizumab and chemotherapy in metastatic metaplastic triple-negative breast cancer: Data from a central European cohort.

Abstract

e13119 Background: Metaplastic triple-negative breast cancer (MpTNBC) is a rare and clinically aggressive subtype of breast cancer associated with poor prognosis. Although immunotherapy combined with chemotherapy has demonstrated clinical benefit in patients with metastatic triple-negative breast cancer (mTNBC), data specific to MpTNBC remain limited. This study aimed to evaluate the real-world efficacy and safety of pembrolizumab in combination with chemotherapy in patients with metastatic MpTNBC. Methods: Within the CEBCC-101 real-world evidence program, a multinational, multicenter retrospective study collecting data from 20 oncology centers across Central Europe, we performed a predefined subanalysis restricted to patients with histologically confirmed metaplastic MpTNBC treated with first-line pembrolizumab plus chemotherapy in routine practice (outside clinical trials). Among 178 women with mTNBC included in CEBCC-101, 14 MpTNBC cases (7.9%) were identified across 9 oncology centers and constituted the study population for the present analysis. Treatment was initiated in Poland, the Czech Republic and Slovakia between September 2022 and June 2025. Safety was assessed as the incidence and severity of treatment-emergent adverse events (AEs), graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The median age at treatment initiation was 59.7 years (range, 33.1–81.0). The median follow-up was 14.0 months (range, 7.5–20.4). At data cutoff, 13 patients had discontinued treatment due to disease progression (n = 11) or treatment-related toxicity (n = 2), while one patient remained on therapy; 11 patients had died. Objective response rate (ORR) was observed in 7 of 14 patients (50.0%), and disease control rate (DCR) was achieved in 11 patients (78.6%). Median overall survival (mOS) was 14.1 months, with 6-, 12-, and 18-month OS rates of 100.0%, 64.3%, and 40.2%, respectively. Median progression-free survival (mPFS) was 6.0 months, with corresponding PFS rates of 50.0%, 14.3%, and 7.1%. Grade ≥2 AEs occurred in 12 patients (85.7%). Grade 3 toxicity was observed in 6 (42.9%), with no grade 4–5 events reported. The most frequent AEs were chemotherapy-related, predominantly neutropenia and peripheral neuropathy. Conclusions: This first international real-world series evaluates pembrolizumab in combination with chemotherapy in patients with metastatic MpTNBC. mPFS and mOS observed in this real-world cohort were markedly shorter than those reported in the phase III KEYNOTE-355 trial, most likely reflecting the exceptionally aggressive clinical course of MpTNBC. The safety profile of treatment was acceptable. These findings underscore the need for further prospective studies and international collaboration in rare breast cancer subtypes.