Pembrolizumab for Early Triple‑Negative Breast Cancer
Pembrolizumab combined with neoadjuvant chemotherapy significantly increases the rate of pathological complete response in patients with early triple‑negative breast cancer.
BACKGROUND: Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple‑negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple‑negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear. METHODS: In this phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with previously untreated stage II or stage III triple‑negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) every 3 weeks plus paclitaxel and carboplatin (784 patients; the pembrolizumab‑chemotherapy group) or placebo every 3 weeks plus paclitaxel and carboplatin (390 patients; the placebo‑chemotherapy group); the two groups then received an additional four cycles of pembrolizumab or placebo, and both groups received doxorubicin‑cyclophosphamide or epirubicin‑cyclophosphamide. After definitive surgery, the patients received adjuvant pembrolizumab or placebo every 3 weeks for up to nine cycles. The primary end points were a pathological complete response at the time of definitive surgery and event‑free survival in the intention‑to‑treat population. RESULTS: At the first interim analysis, among the first 602 patients who underwent randomization, the percentage of patients with a pathological complete response was 64.8% (95% CI, 59.9 to 69.5) in the pembrolizumab‑chemotherapy group and 51.2% (95% CI, 44.1 to 58.3) in the placebo‑chemotherapy group (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P<0.001). After a median follow‑up of 15.5 months (range, 2.7 to 25.0), 58 of 784 patients (7.4%) in the pembrolizumab‑chemotherapy group and 46 of 390 patients (11.8%) in the placebo‑chemotherapy group had disease progression that precluded definitive surgery, had local or distant recurrence or a second primary tumor, or died from any cause (hazard ratio, 0.63; 95% CI, 0.43 to 0.93). Across all treatment phases, the incidence of treatment‑related adverse events of grade 3 or higher was 78.0% in the pembrolizumab‑chemotherapy group and 73.0% in the placebo‑chemotherapy group, including death in 0.4% (3 patients) and 0.3% (1 patient), respectively. CONCLUSIONS: Among patients with early triple‑negative breast cancer, the percentage with a pathological complete response was significantly higher among those who received pembrolizumab plus neoadjuvant chemotherapy than among those who received placebo plus neoadjuvant chemotherapy.
The study demonstrates that adding pembrolizumab to standard neoadjuvant chemotherapy yields a substantially higher pathological complete response rate in early triple‑negative breast cancer, suggesting a meaningful therapeutic advance that could translate into improved long‑term outcomes for this aggressive disease.
Bizonyítékszint: Irányelv / elfogadott gyakorlat. Magas szintű klinikai elfogadottság.
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- Clinical Trials in Cancer - Transforming Clinical Research in the United States - NCBI Bookshelf
- Decoding Clinical Trials in Metastatic Breast Cancer: Practical Insights for Optimal Therapy Sequencing
- The SURVIVE study (NCT05658172): Bringing breast cancer aftercare to the 21st century: Study protocol of a Phase III clinical trial comparing liquid biopsy guided vs. Standard of care surveillance for intermediate to high-risk breast cancer survivors - PMC