Timing of Recurrence After Neoadjuvant Chemo-Immunotherapy in Early-Stage Triple-Negative Breast Cancer.

Introduction: Neoadjuvant chemo-immunotherapy for high-risk triple-negative breast cancer (TNBC) has been shown to reduce the risk of recurrence and improve survival. However, the prognosis for patients with metastatic TNBC remains poor, especially for those with an early recurrence, who represent an urgent unmet need. Defining the most common timing of recurrences after chemo-immunotherapy is crucial for shaping the design of future clinical trials.

Methods: We analyzed five clinical trials of neoadjuvant chemo-immunotherapy in early-stage TNBC to quantify the contribution of early recurrences (within 24 months from randomization) to the overall risk of relapse. Event-free survival data were extracted from Kaplan-Meier curves using PlotDigitizer. Events were evaluated up to 48 months, a time frame with consistent follow-up across trials and minimal later events. The primary endpoint was the proportion of early versus total recurrences by 48 months; secondary analyses stratified this by pathological complete response status.

Results: Overall recurrence rates by 48 months in the immunotherapy arms were: 14.3% (GeparNuevo), 14.8% (NSABP-B59/GeparDouze), 17.5% (KEYNOTE-522), 20.2% (IMpassion031), and 29.2% (NeoTRIP). The proportion of early relapse ranged from 64.6% in NSABP-B59/GeparDouze to 82.9% in GeparNuevo. This proportion was higher in patients with residual disease after neoadjuvant therapy (range 69.4% to 88.6%). Patients who achieved a pathological complete response showed a similar proportion of early and late events.

Conclusions: Recurrences within 24 months account for majority of recurrences in TNBC patients who relapse after neoadjuvant chemo-immunotherapy. Clinical trials are needed to define the optimal therapy for this patient population.