Impact of Immunotherapy Addition on Dose Density and Clinical Outcomes of Neoadjuvant Chemotherapy for Triple-negative Breast Cancer: A Retrospective, Real-world Study From Multiple Centers in London, UK.

BACKGROUND

Neoadjuvant chemotherapy (NACT) combined with pembrolizumab is now standard care for early-stage, triple-negative breast cancer (TNBC), based on KEYNOTE-522 demonstrating improved pathological complete response (pCR), event-free survival, and overall survival. However, the real-world impact of treatment modifications due to toxicity remains unclear. We evaluated clinical outcomes and treatment delivery in routine practice.

MATERIALS AND

METHODS

This multicenter retrospective study included patients with stage II to III TNBC treated with NACT plus pembrolizumab across 5 UK centers (May 2022-June 2025). Data on immune-related adverse events (irAES), corticosteroid use, immunotherapy omissions, chemotherapy dose reductions and recurrence were collected. pCR rates were compared according to treatment modifications.

RESULTS

One hundred patients were analyzed (median age 50 years; 54% node-positive). Overall pCR rate was 54.0%, with no significant difference by pembrolizumab omissions (0: 55.0%; 1-3: 55.6%; ≥ 4: 46.2%; P = .83) or corticosteroid use (48.3% vs. 56.3%; P = .61). Grade ≥ 3 toxicities occurred in 37%, and 29% required corticosteroids, most commonly between cycles 2 to 4. Pembrolizumab omissions occurred in 40%, chemotherapy dose reductions in 57%; 23% did not complete planned chemotherapy. Fourteen recurrences were observed (median 11 months), predominantly in baseline node-positive disease; 4 occurred despite pCR.

CONCLUSIONS

In real-world practice, pembrolizumab-based NACT is associated with frequent treatment modification, yet pCR rates remain comparable to trial data. Early recurrences-often in node-positive patients and occasionally despite pCR-highlight the need for improved risk stratification, optimized adjuvant strategies, and proactive toxicity management to ameliorate long-term outcomes.