Palbociclib for Hormone-Receptor–Positive, HER2-Positive Advanced Breast Cancer

作者：Otto Metzger, Sumithra Mandrekar, Shom Goel, J. Gligorov, Elgene Lim, Eva Ciruelos, Sibylle Loibl, Travis Dockter, Xavier Gonzàlez Farré, Prudence A. Francis, Filipa C. Lynce, Jane Lanzillotti, Carter DuFrane, Anna K. M. Wall, Carrie A. Strand, Ian E. Krop, Ines Vaz-Luis, Debu Tripathy, Sherene Loi, Aleix Prat, Matthew Goetz, Santiago Escrivá-de-Romaní, David J.T. Porter, Jennifer Spoenlein, Daniel G. Stover, Sagar D. Sardesai, Pierre‐Etienne Heudel, Maria T. Koehler, Cynthia Huang Bartlett, Ariadna Holynskyj, Prashanth Gopalakrishna, Eric Roland Gauthier, Suzette Delaloge, Kathy Miller, Eric P. Winer, Luca Gianni, Ann H. Partridge, Angela M. DeMichele, Lisa A. Carey · 发表于：New England Journal of Medicine · 年份：2026 · DOI：10.1056/nejmoa2511218 · 被引用次数：37 · 研究领域：Advanced Breast Cancer Therapies、HER2/EGFR in Cancer Research、Cancer-related Molecular Pathways

BACKGROUND: Dual anti-human epidermal growth factor receptor 2 (HER2) therapy plus chemotherapy followed by maintenance treatment with HER2-targeted and endocrine therapies is standard first-line treatment for hormone-receptor-positive, HER2-positive metastatic breast cancer. On the basis of preclinical and clinical data, the addition of palbociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) may overcome resistance to both endocrine and HER2-directed therapies. METHODS: In this phase 3, open-label, randomized trial, we enrolled patients with hormone-receptor-positive, HER2-positive metastatic breast cancer who did not have disease progression after four to eight cycles of chemotherapy plus HER2-targeted therapy. Patients were randomly assigned in a 1:1 ratio to receive maintenance HER2-targeted and endocrine therapies with or without palbociclib. The primary end point was investigator-assessed progression-free survival. Secondary end points included the objective response, clinical benefit, safety, and overall survival. RESULTS: A total of 518 patients underwent randomization: 261 were assigned to receive palbociclib and 257 to receive standard therapy. At a median follow-up of 53.5 months, patients in the palbociclib group had significantly longer progression-free survival than those in the standard-therapy group (median duration, 44.3 months vs. 29.1 months; hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; two-side...