Maintenance Palbociclib Extends Progression-Free Survival in HR-Positive, HER2-Positive Metastatic Breast Cancer

Clinical Summary: 

• Design/Population: The phase 3 PATINA trial evaluated maintenance palbociclib plus anti-HER2 and endocrine therapy versus anti-HER2 and endocrine therapy alone in patients with HR-positive, HER2-positive metastatic breast cancer who had no disease progression following first-line induction chemotherapy and HER2-targeted therapy.
• Key Outcomes: Adding palbociclib significantly prolonged progression-free survival compared with standard maintenance therapy. Although grade ≥3 adverse events were more common with palbociclib, the safety profile was consistent with previous experience, with neutropenia as the predominant toxicity.
• Clinical Relevance: These findings support incorporating palbociclib into first-line maintenance therapy for patients with HR-positive, HER2-positive metastatic breast cancer to extend disease control while emphasizing the importance of toxicity monitoring.

Results from the phase 3 PATINA trial demonstrated that adding palbociclib to maintenance anti-HER2 and endocrine therapy significantly prolonged progression-free survival (PFS) compared with standard maintenance therapy in patients with 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 first-line HER2-targeted therapy plus chemotherapy were randomized 1:1 to receive maintenance anti-HER2 and endocrine therapy with palbociclib (n = 261) or maintenance anti-HER2 and endocrine therapy alone (n = 257). The primary end point was PFS. A key secondary end point was safety. 

After a median follow-up of 53.5 months, median PFS was 44.3 months with palbociclib compared with 29.1 months with standard maintenance therapy (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% of those receiving standard therapy, while grade 4 adverse events occurred in 10% and 3.6% of patients, respectively. Neutropenia was the most frequently reported 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