Anthracycline- and immunotherapy-free neoadjuvant chemotherapy versus KEYNOTE-522 regimen in early-stage triple-negative breast cancer.

Abstract

e12647 Background: Neoadjuvant chemotherapy (NACT) is standard of care in early-stage triple-negative breast cancer (TNBC), with pathologic complete response (pCR) as a surrogate endpoint. KEYNOTE-522 demonstrated improved outcomes with pembrolizumab added to anthracycline–taxane–platinum chemotherapy. However, the comparative benefit of this approach versus anthracycline- and immunotherapy-free regimens remains unclear. Methods: This single-center observational study included consecutive patients with stage II–III TNBC treated with NACT between 2021 and 2024. One group received carboplatin–docetaxel (CbT) plus pegfilgrastim, and the other received the KEYNOTE-522 regimen. Pathologic response was assessed using pCR (RCB 0) and RCB 0–1. Radiologic response, grade ≥3 toxicity, and treatment discontinuation were analyzed. Results: Seventy-four patients were included; 36 received pembrolizumab plus chemotherapy and 38 received CbT. Median age was 53 years; most patients had ECOG PS 0–1. Pathologic response was evaluable in 63 patients. Overall pCR rate was 61.9%. pCR was significantly higher with pembrolizumab compared with chemotherapy alone (79.2% vs 51.3%; OR 3.61, 95% CI 1.12–11.61; p = 0.027). Stage-stratified analysis showed higher pCR rates with pembrolizumab across both stage II and III disease, with the greatest absolute benefit in stage II. A higher rate of favorable pathologic response (RCB 0–1) was also observed with pembrolizumab (79.2% vs 56.4%; OR 2.94). Complete radiologic response was similar between groups (50.0% vs 48.7%). Grade ≥3 adverse events occurred more frequently with pembrolizumab (41.7% vs 28.2%; OR 1.82), mainly myelotoxicity and asthenia, but toxicity was manageable with low treatment discontinuation rates (8.3% vs 7.7%; OR 1.09). No treatment-related deaths or severe immune-related adverse events were observed. At data cutoff, follow-up was short and no significant differences in disease-free or overall survival were detected. Conclusions: In this real-world cohort, pembrolizumab added to neoadjuvant chemotherapy significantly increased pCR and RCB 0–1 rates with acceptable safety. Platinum-based anthracycline- and immunotherapy-free chemotherapy showed encouraging activity and may represent a valid alternative for selected patients unfit for standard regimens. These findings warrant validation in prospective studies. pCR by treatment group (χ² test, p = 0.027). Carboplatine- Docetaxel Pembrolizumab- Carboplatine - Docetaxel Total pCR NO 48,7 % (n 19) 20,8 (n 5) 38,1% YES 51,3% (n 39) 79,2 % (n 24) 61,9%