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

新辅助化疗联合帕博利珠单抗治疗三阴性乳腺癌的真实世界安全性和有效性

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Abstract

BACKGROUND: Neoadjuvant chemotherapy (NAC) with the addition of pembrolizumab has become the standard of care for early-stage II-III triple-negative breast cancer (TNBC). The real-world safety of this regimen is critical to assess in this subset of patients treated with curative intent, since many of the immune-related events observed can be long-lasting or irreversible. PATIENTS AND METHODS: We retrospectively analyzed the medical records for the initial 100 patients with early-stage TNBC treated with NAC and pembrolizumab at a single comprehensive cancer center between April 2022 and April 2023. We used descriptive analyses to assess treatment exposure, real-world safety and effectiveness of this combination. Treatment-related toxicities were reported according to the Common Terminology Criteria for Adverse Events v5.0. Follow-up extended until the end of the adjuvant phase. RESULTS: The median age of the patients was 52 years, and 21% were identified as germline pathogenic BRCA1 /2 alteration carriers. Treatment discontinuation rate due to adverse events (AEs) in the neoadjuvant phase was 35%. Half of the patients (50%) required dose reductions of at least one chemotherapy drug. The total rate of pathological complete response/residual cancer burden 0 was 58%. A total of 61% experienced at least one immune-related AE (irAE), 30% of which were grade 3-5. We documented one grade 5 toxicity following immune-related myocarditis. CONCLUSION: In this real-life cohort, treatment discontinuation was frequent and linked to treatment toxicity of either chemotherapy or pembrolizumab. We report a higher rate of all grade and grade ≥3 irAEs as compared to the rates documented in the pivotal KEYNOTE 522 trial. The effectiveness of neoadjuvant chemo-immunotherapy for the treatment of stage II-III TNBC was similar to that reported in the literature.

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