Efficacy and safety of neoadjuvant chemotherapy combination with pembrolizumab in triple-negative breast cancer: Real-world data

Neoadjuvant chemotherapy (NAC) with the addition of Pembrolizumab (anti-PD1) is the current standard of care for early-stage II-III triple-negative breast cancer (TNBC). Although immunotherapy improves efficacy, toxicity rates remain a paramount parameter to consider since many of the events are long-lasting for this subset of patients (pts) treated with a curative intent. We conducted a retrospective analysis of the medical records of 95 pts with early-stage TNBC treated with NAC and Pembrolizumab, between April 2022 and April 2023 in our institution. At the time of this submission, the toxicity analysis is available for 74 pts and efficacy for 64 pts. A complete analysis of 95 pts will be presented at ESMO. Treatment-related toxicities are reported according to the common terminology criteria for adverse events (CTCAE) v5.0. The cohort currently comprises 74 female patients, with a median age of 50 years [20-74]; 52% were premenopausal, and 20% harboured a deleterious BRCA germline mutation. Efficacy analysis (n=64): Pathologic complete response (pCR) rate was 56 % (n=36). The rate of pCR in pts with BRCA1/2 germline mutations was 80% (n=12). Toxicity analysis (n=74): We reported 376 toxicity events, of which 27% were grade 3-4. Most events were attributed to chemotherapy (55%). The immune-related adverse events (irAE) rate was 26%. A total of 35% of pts discontinued treatment due to toxicity, most commonly: liver toxicity, recurrent severe haematological and severe skin toxicities; while 50% of pts required dose reductions. The most common grade 3-4 AEs were neutropenia in 49% of pts and hepatic toxicity in 30% of cases. Immune-mediated thyroid dysfunction occurred in 25.7%, adrenal insufficiency was witnessed in 5%(4) of pts and hypophysitis in 4%(3). Immune-mediated myocarditis was witnessed in 1 elderly patient. In this real-life cohort of early-stage TNBC patients treatment with a chemo-immunotherapy combination in the neoadjuvant setting was effective. However, we witnessed an important rate of treatment discontinuation due to toxicity. The impact on the quality of life of these patients should be carefully evaluated, especially in regard to permanent toxicities.