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

Metzger, O; Mandrekar, S; Goel, S; Gligorov, J; Lim, E; Ciruelos, E; Loibl, S; Dockter, T; Gonz&#224;lez Farr&#233;, X; Francis, PA; Lynce, F; Lanzillotti, J; DuFrane, C; Wall, A; Strand, C; Krop, I; Vaz-Luis, I; Tripathy, D; Loi, S; Prat, A; Goetz, M; Escriv&#225;-de-Roman&#237;, S; Porter, D; Spoenlein, J; Stover, DG; Sardesai, S; Heudel, P; Koehler, M; Huang Bartlett, C; Holynskyj, A; Gopalakrishna, P; Gauthier, E; Delaloge, S; Miller, K; Winer, EP; Gianni, L; Partridge, AH; DeMichele, A; Carey, LA

Author(s): Metzger, O; Mandrekar, S; Goel, S; Gligorov, J; Lim, E; Ciruelos, E; Loibl, S; Dockter, T; Gonzàlez Farré, X; Francis, PA; Lynce, F; Lanzillotti, J; DuFrane, C; Wall, A; Strand, C; Krop, I; Vaz-Luis, I; Tripathy, D; Loi, S; Prat, A; Goetz, M; Escrivá-de-Romaní, S; Porter, D; Spoenlein, J; Stover, DG; Sardesai, S; Heudel, P; Koehler, M; Huang Bartlett, C; Holynskyj, A; Gopalakrishna, P; Gauthier, E; Delaloge, S; Miller, K; Winer, EP; Gianni, L; Partridge, AH; DeMichele, A; Carey, LA;
Details: Publication Year 2026-01-29,Volume 394,Issue #5,Page 451-462
Journal Title: New England Journal of Medicine
Publication Type: Research article
Abstract: 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-sided P = 0.02). Grade 3 and 4 adverse events, predominantly from neutropenia, occurred in 79.7% and 10.0% of the patients, respectively, in the palbociclib group, as compared with 30.6% and 3.6% of the patients, respectively, in the standard-therapy group. CONCLUSIONS: The addition of palbociclib to maintenance anti-HER2 and endocrine therapies led to a significant improvement in progression-free survival over standard therapy, with increased toxic effects, mainly neutropenia. (Funded by Pfizer and others; PATINA ClinicalTrials.gov number, NCT02947685.).
Publisher: Massachusetts Medical Society
Keywords: Adult; Aged; Aged, 80 and over; Female; Humans; Middle Aged; *Antineoplastic Combined Chemotherapy Protocols/adverse; effects/pharmacology/therapeutic use; *Breast Neoplasms/drug therapy/mortality/pathology; Cyclin-Dependent Kinase 4/antagonists & inhibitors; Cyclin-Dependent Kinase 6/antagonists & inhibitors; *Erb-b2 Receptor Tyrosine Kinases/antagonists & inhibitors/analysis; *Piperazines/adverse effects/pharmacology/therapeutic use; Progression-Free Survival; *Protein Kinase Inhibitors/adverse effects/pharmacology/therapeutic use; *Pyridines/adverse effects/pharmacology/therapeutic use; Receptors, Estrogen/analysis/antagonists & inhibitors; Drug Resistance, Neoplasm/drug effects; Antineoplastic Agents, Hormonal/pharmacology/therapeutic use; Maintenance Chemotherapy/adverse effects/methods; Neutropenia/chemically induced/epidemiology; Male; *Breast Neoplasms, Male/drug therapy/mortality/pathology; Follow-Up Studies
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1056/NEJMoa2511218
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-02-03 06:11:42

Last Modified: 2026-02-03 06:11:50