Effectiveness and Toxicity Burden of Pembrolizumab in Combination With Neoadjuvant Chemotherapy for Stage II/III Triple Negative Breast Cancer: A Real-World Analysis From Alberta, Canada

OBJECTIVES: The KEYNOTE-522 trial demonstrated improved pathologic complete response (pCR) and long-term survival outcomes by adding pembrolizumab to neoadjuvant anthracycline and taxane (A-T) plus carboplatin in patients with stage II/III triple-negative breast cancer (TNBC). We evaluated early effectiveness and toxicity burden of adding pembrolizumab and carboplatin to neoadjuvant A-T in patients with stage II/III TNBC. METHODS: We included all patients in Alberta with stage II/III TNBC from November 2020 to November 2023, treated with either neoadjuvant A-T or the KEYNOTE-522 regimen, and who underwent surgical resection by June 1, 2024. Our primary outcome was pCR, while secondary outcomes included rates of breast-conserving surgery (BCS), axillary lymph node dissection (ALND), toxicity burden during the neoadjuvant phase, and receipt/type of adjuvant therapy. Propensity score matching (PSM) was conducted to account for baseline differences between groups. RESULTS: A total of 248 patients were included (110 A-T and 138 KEYNOTE-522). Before PSM, the KEYNOTE-522 group had higher rates of pCR (64% vs. 32%; P<0.001) and BCS (57% vs. 42%; P=0.022) with lower rates of ALND (15% vs. 40%; P<0.001). The KEYNOTE-522 group had more emergency department visits (47% vs. 31%, P=0.010) and hospitalizations (23% vs. 6%, P<0.001). After PSM, baseline characteristics between groups were balanced, and differences in effectiveness and toxicity burden outcomes persisted. Within the KEYNOTE-522 group, 70% had postoperative pembrolizumab. CONCLUSIONS: Proportions of pCR and BCS were higher, and ALND lower, in KEYNOTE-522 treated patients with stage II/III TNBC, even after PSM. Future evaluation is needed to determine the real-world impact of the KEYNOTE-522 regimen on recurrence and survival.