Pembrolizumab and chemotherapy in high-risk, early-stage, ER+/HER2− breast cancer: a randomized phase 3 trial
Mené sur 1 278 patientes atteintes d'un cancer du sein ER+ HER2- de stade précoce et à haut risque de récidive, cet essai de phase III évalue l'efficacité, du point de vue du taux de réponse pathologique complète et de la survie sans événement, et la toxicité de l'ajout du pembrolizumab à une chimiothérapie néoadjuvante
Résumé en anglais
Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER+/HER2− grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1–2 or T3–4, cN0–2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W. After surgery (with/without adjuvant radiation therapy), patients received adjuvant pembrolizumab or placebo for nine cycles plus adjuvant endocrine therapy. Dual primary endpoints were pathological complete response and event-free survival in the intention-to-treat population. In total, 635 patients were assigned to the pembrolizumab−chemotherapy arm and 643 to the placebo−chemotherapy arm. At the study’s prespecified first interim analysis, the pathological complete response rate was 24.3% (95% confidence interval (CI), 21.0–27.8%) in the pembrolizumab−chemotherapy arm and 15.6% (95% CI, 12.8–18.6%) in the placebo−chemotherapy arm (estimated treatment difference, 8.5 percentage points; 95% CI, 4.2–12.8; P = 0.00005). Event-free survival was not mature in this analysis. During the neoadjuvant phase, treatment-related adverse events of grade ≥3 were reported in 52.5% and 46.4% of patients in the pembrolizumab−chemotherapy and placebo−chemotherapy arms, respectively. In summary, the addition of pembrolizumab to neoadjuvant chemotherapy significantly improved the pathological complete response rate in patients with high-risk, early-stage ER+/HER2− breast cancer. Safety was consistent with the known profiles of each study treatment. Follow-up continues for event-free survival. ClinicalTrials.gov identifier: NCT03725059.
