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

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.