e12507 Background: The addition of pembrolizumab (PEM) to neoadjuvant chemotherapy (NAC) has been shown to significantly improve pathological complete response (pCR) rates in patients with early-stage triple-negative breast cancer (TNBC). However, long-term prognostic outcomes in real-world clinical practice, specifically for patients who achieve pCR, have not been sufficiently verified. This study evaluated the efficacy and safety of PEM-combined regimens, with a specific focus on the prognostic implications for patients achieving pCR. Methods: We analyzed 219 patients with TNBC who underwent NAC at our institution between 2009 and 2025. Patients were categorized into a conventional chemotherapy group (TN-historical; n=170) and a pembrolizumab combination group (TN-PEM; n=49). Primary endpoints included pCR rates, disease-free survival (DFS), and overall survival (OS). A subgroup analysis was performed on 100 patients who achieved pCR (TN-historical: n=67; TN-PEM: n=33) to evaluate recurrence patterns and post-recurrence survival. Statistical analyses were performed using Fisher's exact test, the Kaplan-Meier method, and the Log-rank test. Results: The overall pCR rate was significantly higher in the TN-PEM group compared to the TN-historical group (67.3% vs. 39.4%; p=0.001). However, among patients who achieved pCR, long-term outcomes were unexpectedly inferior in the immunotherapy cohort. The 5-year DFS rate for pCR achievers was 81.8% in the TN-PEM group versus 96.6% in the TN-historical group (p=0.002). Similarly, the 5-year OS rate was significantly lower in the TN-PEM group (76.9% vs. 100.0%; p=0.001). The recurrence rate among pCR cases was significantly higher in the TN-PEM group (15.2% 5/33) compared to the TN-historical group (1.5% 1/67; p=0.014). Notably, 80% of recurrences in the TN-PEM group involved liver metastases. The clinical course after recurrence in the TN-PEM group was aggressive, with a median time from recurrence to death of only 2.7 months. Conclusions: While the addition of pembrolizumab to NAC significantly improves pCR rates in TNBC, our data suggest a paradoxical risk of early and aggressive recurrence even after achieving pCR. Recurrences in the PEM-treated cohort were characterized by a high incidence of liver metastasis and rapid disease progression, suggesting potential acquired resistance mechanisms following immunotherapy. These findings underscore the necessity for rigorous surveillance and the development of novel therapeutic strategies for patients treated with immune checkpoint inhibitors, regardless of pathological response status.
Fujisawa et al. (Thu,) studied this question.