Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer

Schmid, P.; Cortes, J.; Dent, R.; Pusztai, L.; McArthur, H.; Kummel, S.; Bergh, J.; Denkert, C.; Park, Y. H.; Hui, R.; Harbeck, N.; Takahashi, M.; Untch, M.; Fasching, P. A.; Cardoso, F.; Andersen, J.; Patt, D.; Danso, M.; Ferreira, M.; Mouret-Reynier, M.-A.; Im, S.-A.; Ahn, J.-H.; Gion, M.; Baron-Hay, S.; Boileau, J.-F.; Ding, Y.; Tryfonidis, K.; Aktan, G.; Karantza, V. und O'Shaughnessy, J. (2022): Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. In: New England Journal of Medicine, Bd. 386, Nr. 6: S. 556-567

Abstract

BACKGROUND The addition of pembrolizumab to neoadjuvant chemotherapy led to a significantly higher percentage of patients with early triple-negative breast cancer having a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery in an earlier analysis of this phase 3 trial of neoadjuvant and adjuvant therapy. The primary results regarding event-free survival in this trial have not been reported. METHODS We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response (the results for which have been reported previously) and event-free survival, defined as the time from randomization to the date of disease progression that precluded definitive surgery, local or distant recurrence, occurrence of a second primary cancer, or death from any cause. Safety was also assessed. RESULTS Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. The median follow-up at this fourth planned interim analysis (data cutoff, March 23, 2021) was 39.1 months. The estimated event-free survival at 36 months was 84.5% (95% confidence interval (CI], 81.7 to 86.9) in the pembrolizumab-chemotherapy group, as compared with 76.8% (95% CI, 72.2 to 80.7) in the placebo-chemotherapy group (hazard ratio for event or death, 0.63;95% CI, 0.48 to 0.82;P<0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy. CONCLUSIONS In patients with early triple-negative breast cancer, neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab after surgery, resulted in significantly longer event-free survival than neoadjuvant chemotherapy alone.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0028-4793
• Sprache: Englisch