RCT: Pembrolizumab Plus Chemotherapy Improved Overall Survival in Early-Stage Triple-Negative Breast Cancer
18 Sep, 2024 | 16:08h | UTCBackground: Early-stage triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor prognosis. The phase 3 KEYNOTE-522 trial previously demonstrated that adding pembrolizumab to chemotherapy improved pathological complete response rates and event-free survival in this population.
Objective: To determine whether neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab improves overall survival compared to neoadjuvant chemotherapy alone in patients with early-stage TNBC.
Methods: In this multicenter, randomized, double-blind, placebo-controlled phase 3 trial (KEYNOTE-522), 1174 patients with previously untreated stage II or III TNBC were randomized 2:1 to receive neoadjuvant pembrolizumab (200 mg every 3 weeks) plus chemotherapy (paclitaxel and carboplatin, followed by doxorubicin–cyclophosphamide or epirubicin–cyclophosphamide) or placebo plus the same chemotherapy regimen. After surgery, patients received adjuvant pembrolizumab or placebo every 3 weeks for up to nine cycles. The primary endpoints were pathological complete response and event-free survival; overall survival was a key secondary endpoint.
Results: After a median follow-up of 75.1 months, the estimated 5-year overall survival was 86.6% in the pembrolizumab–chemotherapy group versus 81.7% in the placebo–chemotherapy group (hazard ratio for death, 0.66; P=0.002). The 5-year event-free survival was 81.2% versus 72.2%, respectively (hazard ratio for event or death, 0.65; 95% CI, 0.51–0.83). Grade 3 or higher treatment-related adverse events occurred in 77.1% of patients receiving pembrolizumab–chemotherapy and 73.3% receiving placebo–chemotherapy. Serious treatment-related adverse events occurred in 34.1% and 20.1% of patients, respectively.
Conclusions: Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab significantly improved overall survival compared to chemotherapy alone in patients with early-stage TNBC.
Implications for Practice: The addition of pembrolizumab to standard neoadjuvant chemotherapy, followed by adjuvant pembrolizumab, should be considered a new standard of care for patients with high-risk, early-stage TNBC, offering a significant survival benefit.
Study Strengths and Limitations: Strengths include the large, international, randomized design, the use of a placebo control, and long-term follow-up. Limitations include the inability to isolate the effects of neoadjuvant versus adjuvant pembrolizumab and the exclusion of adjuvant capecitabine from the treatment protocol.
Future Research: Further studies should focus on identifying biomarkers predictive of response to pembrolizumab, optimizing the sequencing and duration of immunotherapy, and evaluating the addition of other agents to improve outcomes in early-stage TNBC.