Long-term outcomes in triple-negative breast cancer after a pathologic complete response: does the type of neoadjuvant therapy matter?

Abstract

Background: Neoadjuvant chemotherapy is standard for stage IB-III triple-negative breast cancer (TNBC), with pathological complete response (pCR) strongly associated with survival. Although escalation with platinum and immune checkpoint inhibitors (ICI) improves pCR and long-term outcomes, patients with pCR in control arms of pivotal trials also show favorable outcomes. Whether the regimen leading to pCR impacts long-term survival is largely unknown.

Methods: We conducted a systematic review and meta-analysis, searching phase II and III trials including early-stage TNBC patients with pCR. A pooled analysis of Kaplan-Meier-derived individual patient data was performed for event-free survival (EFS) and overall survival (OS), with subgroup analyses by treatment regimens.

Results: Of 2830 identified publications, 18 trials comprising 3430 patients were included. Neoadjuvant ICI with chemotherapy improved EFS (HR 0.67; 95%CI 0.50-0.89; p < 0.01) compared with chemotherapy-only regimens, with no significant OS difference (HR 0.84; 95%CI 0.50-1.41; P = 0.51). In contrast, EFS and OS were not significantly different regardless of platinum use (HR 0.55; 95%CI 0.20-1.50; P = 0.24 and HR 0.33; 95%CI 0.09-1.22; P = 0.10, respectively). Similarly, anthracycline-containing regimens showed comparable EFS to anthracycline-free regimens (HR 0.86; 95%CI 0.51-1.45; P = 0.58). For patients with pCR after ICI therapy, no benefit of adjuvant ICI for EFS or OS was observed (HR 1.16; 95%CI 0.55-2.44; P = 0.70 and HR 2.91; 95%CI 0.40-21.37; P = 0.29, respectively).

Conclusion: These findings suggest that the context in which a pCR is achieved may influence long-term outcomes. Neoadjuvant ICI-based regimens improve EFS in patients with early-stage TNBC and pCR. However, EFS seems not to be impacted by neoadjuvant chemotherapy type.