No difference was seen in patients who achieved a pathologic complete response between the groups. In addition, distant recurrence at 1 year was also lower in the pembrolizumab plus chemotherapy group. The hazard ratio of 0.63 was significant and indicated that the risk for disease progression was 37% lower with pembrolizumab plus chemotherapy than with placebo plus chemotherapy. The use of pembrolizumab prolonged EFS across the various subgroups of TNBC. Neoadjuvant pembrolizumab plus chemotherapy led to a higher percentage of pathologic complete response than the chemotherapy plus placebo, independent of PD-L1 expression. This study evaluated the efficacy of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab plus chemotherapy in early-stage TNBC. Event-free survival with pembrolizumab in early triple-negative breast cancer. Source: Schmid P, Cortes J, Dent R for the KEYNOTE-522 investigators. “The results of this trial support the use of pembrolizumab plus platinum-, taxane-, and anthracycline-containing neoadjuvant chemotherapy, followed by adjuvant pembrolizumab after surgery, as a treatment regimen for patients with high-risk, early triple-negative breast cancer, regardless of tumor PD-L1 expression status,” the researchers concluded. Treatment-related AEs led to 4 deaths in the pembrolizumab arm and to 1 death in the placebo arm. The rate of immune-mediated AEs of any grade was 33.5% in the pembrolizumab arm and 11.3% in the placebo arm, including 12.9% and 1.0% grade ≥3, respectively. In the combined neoadjuvant and adjuvant phases, grade 3 or 4 AEs were observed in 77.1% of patients in the pembrolizumab plus chemotherapy group and in 73.3% of patients in the placebo plus chemotherapy group. No new safety concerns were identified with the pembrolizumab regimen. At a median follow-up of 39.1 months, 15.7% in the pembrolizumab plus chemotherapy group and 23.8% in the placebo plus chemotherapy group had an adverse event (AE) or died (hazard ratio, 0.63 95% confidence interval, 0.48-0.82 P <.001). The OS data were not mature at the time of the analysis. In the EFS analysis, the most common event was distant recurrence (7.7 vs 13.1, respectively). The estimated EFS at 36 months was 84.5% in the pembrolizumab plus chemotherapy group and 76.8% in the placebo plus chemotherapy group the median EFS was not reached in either group. RESULTS: The study enrolled 1174 patients with stage II or stage III TNBC. The primary end points were pathologic complete response or event-free survival (EFS). After undergoing definitive surgery, patients received adjuvant pembrolizumab plus chemotherapy or placebo plus chemotherapy every 3 weeks, for up to 9 cycles. Patients were randomized (2:1) to neoadjuvant therapy with 4 cycles of pembrolizumab (200 mg) plus paclitaxel and carboplatin or to placebo plus paclitaxel and carboplatin every 3 weeks, followed by 4 cycles of pembrolizumab plus doxorubicin and cyclophosphamide or epirubicin and cyclophosphamide or to placebo plus these chemotherapies. The study included a neoadjuvant phase and an adjuvant phase, as well as a control group. METHODS: KEYNOTE-522 was a prospective, randomized, placebo-controlled, phase 3 clinical trial that compared the benefits of the PD-1 inhibitor pembrolizumab plus chemotherapy versus placebo plus chemotherapy in treatment-naïve patients with early-stage TNBC. Early data for immune checkpoint inhibitors targeting PD-1 or PD-L1 expression in combination with chemotherapy in patients with TNBC have shown antitumor activity. BACKGROUND: The current standard of care for triple-negative breast cancer (TNBC) is chemotherapy with anthracyclines or taxanes, but the overall survival (OS) for this patient population is shorter than the OS in other subtypes of breast cancer, and the risk for disease recurrence or death is high among treatment-naïve patients with stage II or III TNBC.
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