Long-term outcomes of neoadjuvant immunotherapy plus chemotherapy in patients with early-stage triple-negative breast cancer: an extracted individual patient data and trial-level meta-analysis.

TL;DR: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine, and the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy.

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.

TL;DR: This review discusses the efficacy of immune checkpoint inhibitors (ICIs) in triple-negative breast cancer (TNBC), evaluating predictive markers such as PD-L1, tumor mutational burden, and immune cell infiltration, and highlighting clinical progress in combining ICIs with chemotherapy and targeted therapies.

TL;DR: The BrighTNess trial as discussed by the authors showed that the addition of carboplatin with/without veliparib to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) rates with manageable acute toxicity in patients with triple-negative breast cancer (TNBC).

TL;DR: The GeparNuevo trial investigated the addition of durvalumab, an anti-PD-L1 checkpoint inhibitor (CPI), to standard neoadjuvant chemotherapy (NACT) in patients with early TNBC.

TL;DR: The results highlight the importance of neoadjuvant treatment with pembro for improving survival in patients with early TNBC, and identified a subset of pts for whom additional therapies will be needed.

TL;DR: It was found that age <40 years remained significantly associated with poor prognosis in triple negative breast cancer, and both subtypes and age retained their significances in multivariate analysis.