Comparative effectiveness and safety of neoadjuvant chemotherapy in combination with pembrolizumab for triple negative breast cancer: A real-world analysis from Alberta, Canada.

e12629 Background: The KEYNOTE-522 trial demonstrated improved pathologic complete response (pCR) rate and longer-term survival outcomes with the addition of pembrolizumab to neoadjuvant chemotherapy (NAC) which included taxane, carboplatin and anthracycline (TCbA) in patients with stage II/III triple negative breast cancer (TNBC). In Alberta, the KEYNOTE-522 protocol was adopted as standard of care by January 2023. This replaced NAC that routinely included taxane and anthracycline (TA) without carboplatin. This retrospective study describes the real-world clinical impact of adding pembrolizumab and carboplatin to neoadjuvant TA in patients with stage II/III TNBC in Alberta. Methods: The cohort was identified by Alberta Health Services Cancer Research & Analytics and clinical variables were retrieved from electronic medical records.We identified all patients diagnosed with stage II/III TNBC from November 2020 to November 2023 in Alberta, treated with either neoadjuvant TA or TCbA + pembrolizumab, and had undergone surgical resection by June 1, 2024. The primary outcome was rate of pCR. Secondary outcomes included rate of breast conserving surgery (BCS) vs mastectomy, rate of axillary lymph node dissection (ALND) vs sentinel node biopsy, and safety outcomes during the neoadjuvant phase including hospitalizations, emergency visits, and immunotherapy-related adverse events (irAEs). Results: Of the 248 eligible women, 110 were treated with TA and 138 were treated with TCbA + pembrolizumab. There were no differences in clinicopathologic and treatment factors between the groups. Women treated with TCbA + pembrolizumab compared to those treated with TA, had a significant increase in pCR rate of 32% (63.8% vs 31.8%, p < .0001) and BCS rate of 14.7% (56.5% vs 41.8%, p = 0.001) with corresponding 25.5% decrease in the rate of ALND (15.5% vs. 40%, < .0001). Women treated with TCbA + pembrolizumab compared to those with TA, were 16.2% more likely to visit ER (47.1% vs 30.9%, p = 0.009), and 16.1% more likely to be admitted to hospital (22.5% vs 6.4%, p = 0.0005) during the neoadjuvant phase. Among the 138 patients with pembrolizumab, 35 (25.4%) patients developed 46 separate irAEs in the neoadjuvant phase. The most common irAEs related systems were endocrinopathies (32.6%), GI (23%), cutaneous (10.9%), and lung (9%). Conclusions: In this real-world study of stage II/III TNBC, the pCR rate for neoadjuvant TCbA + pembrolizumab was comparable to the intervention arm in KEYNOTE-522 and was significantly improved compared to patients who received TA only. The increased pCR rate corresponded to a higher rate of BCS and lower rate of ALND. Adoption of the KEYNOTE-522 protocol was however associated with significant increased toxicity and use of health care resources, underpinning the need for close clinical management of these patients.