FDA Approves Palbociclib Plus Anti-HER2 and Endocrine Therapy as Maintenance in Breast Cancer

The FDA has approved palbociclib (Ibrance) in combination with trastuzumab (Herceptin), with or without pertuzumab (Perjeta), and endocrine therapy for the maintenance treatment of adults with hormone receptor (HR)–positive, HER2-positive locally advanced or metastatic breast cancer who have not progressed after induction therapy.¹ The combination is indicated for patients with HR-positive, HER2-positive locally advanced or metastatic breast cancer following induction treatment. The approval adds an oral CDK4/6 inhibitor to a maintenance regimen that previously consisted of anti-HER2 therapy and endocrine therapy alone.

The approval was based on findings from PATINA (NCT02947685), a randomized, open-label trial that enrolled 518 patients with HR-positive, HER2-positive locally advanced or metastatic breast cancer who had no evidence of disease progression after induction treatment with a taxane and trastuzumab, with or without pertuzumab. Patients were randomized 1:1 to receive palbociclib with trastuzumab, with or without pertuzumab, and endocrine therapy (fulvestrant or an aromatase inhibitor of anastrozole, letrozole, or exemestane) or to receive trastuzumab, with or without pertuzumab, and endocrine therapy alone, continuing until disease progression or unacceptable toxicity.

The trial's major efficacy outcome measure was investigator-assessed progression-free survival (PFS) by RECIST v1.1, with overall survival as an additional outcome measure. A statistically significant improvement in investigator-assessed PFS was observed with the palbociclib-containing regimen compared with anti-HER2 therapy and endocrine therapy alone (HR, 0.76; 95% CI, 0.59-0.97; 1-sided P =.0134). Median PFS could not be adequately characterized at the time of this analysis because of censoring, and overall survival data remained immature.

Longer-term results reported separately help contextualize the magnitude of benefit. At a later analysis with extended follow-up, median PFS reached 44.3 months in the palbociclib group compared with 29.1 months in the standard-therapy group, corresponding to an estimated 48-month PFS rate of 46.5% vs 38.3%, respectively. The trial enrolled patients who had completed 4 to 8 cycles of induction therapy with trastuzumab and pertuzumab plus a taxane before randomization to maintenance therapy. Findings from PATINA were also presented as late-breaking data at the 2024 San Antonio Breast Cancer Symposium and were subsequently published in The New England Journal of Medicine.²

Safety findings were consistent with the established profile of palbociclib in HER2-negative breast cancer, though the combination was associated with increased toxicity, particularly grade 3 neutropenia, in the experimental arm. The approved prescribing information for palbociclib carries warnings and precautions for neutropenia, interstitial lung disease/pneumonitis, and embryo-fetal toxicity, consistent with labeling for the drug's existing indications.

Dosing and Regulatory Pathway

The recommended dosage of palbociclib is 125 mg orally once daily for 21 consecutive days followed by 7 days off treatment, comprising a 28-day cycle; clinicians should consult the full prescribing information for dosing of trastuzumab, pertuzumab, and endocrine therapy. The FDA noted that its review incorporated the Assessment Aid, a voluntary submission tool used to facilitate the agency's evaluation, and that palbociclib had previously received breakthrough therapy designation for this use. Full prescribing information is expected to be posted on Drugs@FDA^.1

Clinical Context

Palbociclib, a CDK4/6 inhibitor, is already approved in the United States for HR-positive, HER2-negative metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant. PATINA represents the first phase 3 trial to demonstrate benefit from adding a CDK4/6 inhibitor to anti-HER2 and endocrine maintenance therapy in HR-positive, HER2-positive metastatic breast cancer, a population in which resistance to both endocrine and HER2-directed therapy is common. Investigators have suggested the mechanism may involve palbociclib overcoming this dual resistance, although the agent's role relative to other maintenance strategies, and its effect on overall survival, will require longer follow-up to define.

REFERENCES

1. FDA approves palbociclib with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of HR-positive, HER2-positive metastatic breast cancer. US FDA. June 24, 2026. Accessed June 24, 2026. https://tinyurl.com/2dupzx4j

2. Metzger O, Mandrekar S, Goel S, et al. Palbociclib for Hormone-Receptor-Positive, HER2-Positive Advanced Breast Cancer. N Engl J Med. 2026 Jan 29;394(5):451-462. doi: 10.1056/NEJMoa2511218. PMID: 41604639.