Maintenance Palbociclib Extends PFS in HR-Positive, HER2-Positive Metastatic Breast Cancer

Key Clinical Takeaways: 

• Design/Population: The phase 3 PATINA trial enrolled patients with HR-positive, HER2-positive metastatic breast cancer who had no disease progression after 4 to 8 cycles of HER2-targeted therapy plus chemotherapy. Patients were randomized to receive maintenance anti-HER2 and endocrine therapy with or without palbociclib.
• Key Outcomes: Addition of palbociclib significantly improved median progression-free survival compared with standard maintenance therapy. Higher rates of grade 3/4 adverse events, primarily neutropenia, were observed in the palbociclib arm.
• Clinical Relevance: These results support palbociclib as an effective maintenance option to extend disease control in HR-positive, HER2-positive metastatic breast cancer. Careful patient selection and proactive toxicity monitoring are essential to optimize clinical benefit.

Results from the phase 3 PATINA trial demonstrated that the adding palbociclib to maintenance anti-HER2 and endocrine therapy significantly improved progression-free survival (PFS) in patients with hormone receptor (HR)-positive, HER2-positive metastatic breast cancer.

“Dual anti-HER2 therapy plus chemotherapy followed by maintenance treatment with HER2-targeted and endocrine therapies is standard first-line treatment for [HR]-positive, HER2-positive metastatic breast cancer,” stated Otto Metzger, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and coauthors. “On the basis of preclinical and clinical data, the addition of palbociclib may overcome resistance to both endocrine and HER2-directed therapies.”

In this open-label trial, 518 patients without disease progression after 4 to 8 cycles of HER2-targeted therapy plus chemotherapy were randomized 1:1 to receive maintenance HER2-targeted and endocrine therapy with palbociclib (n = 261) or without palbociclib (n = 257). The primary end point was progression-free survival (PFS), and a key secondary end point was safety.

At a median follow-up of 53.5 months, median PFS was 44.3 months in the palbociclib arm and 29.1 months in the standard-therapy arm (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.59 to 0.96; P = .02). Grade 3 adverse events occurred in 79.7% of patients receiving palbociclib compared with 30.6% receiving standard therapy, and grade 4 adverse events occurred in 10% and 3.6% of patients, respectively. Neutropenia was the predominant toxicity associated with palbociclib.

“The addition of palbociclib to maintenance anti-HER2 and endocrine therapies led to a significant improvement in [PFS] over standard therapy, with increased toxic effects, mainly neutropenia,” concluded Dr Metzger et al. 

Source:

Metzger O, Mandrekar S, Goel S, et al. Palbociclib for hormone-receptor-positive, HER2-positive advanced breast cancer. N Engl J Med. Published online: January 28, 2026. doi:10.1056/NEJMoa2511218