FDA Approves Palbociclib-Based Maintenance Regimen for HR-Positive, HER2-Positive Metastatic Breast Cancer

The FDA has approved palbociclib (Ibrance; Pfizer) in combination with trastuzumab (Herceptin, Genentech), with or without pertuzumab (Perjeta, Genentech, Inc.), and endocrine therapy as maintenance treatment for adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer following induction treatment.¹

The approval expands the use of palbociclib into HR-positive, HER2-positive disease and establishes a maintenance strategy that simultaneously targets cyclin-dependent kinases 4 and 6 (CDK4/6), HER2 signaling, and hormone receptor signaling. Palbociclib received breakthrough therapy designation for the indication.¹

Targeting Multiple Drivers of HR-Positive, HER2-Positive Disease

Palbociclib is an orally administered, selective inhibitor of CDK4 and CDK6, proteins that regulate progression through the cell cycle. The inhibition of CDK4/6 reduces retinoblastoma protein phosphorylation and can prevent susceptible tumor cells from progressing from the G1 phase into the S phase, thereby slowing cellular proliferation.²

Palbociclib was initially approved in the United States in 2015 and has been used primarily with endocrine therapy for HR-positive, HER2-negative advanced or metastatic breast cancer. The newly approved regimen extends CDK4/6 inhibition to patients whose tumors are driven by both hormone receptor and HER2 signaling.¹˒²

HR-positive, HER2-positive breast cancer presents a distinct therapeutic challenge because interactions between estrogen receptor and HER2 signaling pathways may contribute to resistance to endocrine and anti-HER2 therapies. The maintenance regimen is designed to provide continued HER2 blockade with trastuzumab, with or without pertuzumab, alongside endocrine therapy while adding palbociclib to inhibit cell-cycle progression.

Patients eligible for the newly approved regimen must have completed induction treatment and have locally advanced or metastatic disease that has not progressed. This approval does not position palbociclib as part of the initial taxane-containing induction regimen.

PATINA Trial Supports Approval

Efficacy was evaluated in PATINA (NCT02947685), a randomized, open-label phase 3 trial that enrolled 518 patients with HR-positive, HER2-positive locally advanced or metastatic breast cancer. The participators had no evidence of disease progression after induction treatment with a taxane and trastuzumab, with or without pertuzumab, for advanced disease.¹˒³

Patients were randomly assigned 1:1 to receive palbociclib plus trastuzumab, with or without pertuzumab, and endocrine therapy or trastuzumab, with or without pertuzumab, and endocrine therapy alone. Permitted endocrine therapies included fulvestrant or an aromatase inhibitor—anastrozole (Arimidex, AstraZeneca), letrozole (Femara, Novartis), or exemestane (Aromasin, Pfizer). Treatment continued until disease progression or unacceptable toxicity.¹

The trial’s primary efficacy end point was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Overall survival (OS) was an additional efficacy outcome.

The addition of palbociclib produced a statistically significant improvement in investigator-assessed PFS compared with anti-HER2 and endocrine maintenance therapy alone. The hazard ratio for disease progression or death was 0.76 (95% CI, 0.59-0.97; 1-sided P = .0134), corresponding to a 24% reduction in the risk of disease progression or death.¹

According to the FDA, median PFS could not be adequately described because of censoring in the regulatory analysis. OS data were not mature at the time of the PFS analysis, and continued follow-up will be needed to determine whether the improvement in disease control translates into an OS benefit.¹

Previously reported results from PATINA also identified hematologic toxicities, particularly neutropenia and leukopenia, as the most frequent adverse events associated with the addition of palbociclib. No new safety signals were identified relative to the established safety profile of the CDK4/6 inhibitor.⁴

Dosing and Safety Considerations

The recommended dosage of palbociclib is 125 mg orally once daily for 21 consecutive days, followed by 7 days without treatment, constituting a 28-day cycle. Clinicians should consult the respective prescribing information for dosing recommendations for trastuzumab, pertuzumab, and the selected endocrine therapy.¹

The palbociclib prescribing information includes warnings and precautions for neutropenia, interstitial lung disease or pneumonitis, and embryo-fetal toxicity.¹ Complete blood cell counts should be monitored before treatment begins, at the start of each cycle, on day 15 of the first 2 cycles, and as clinically indicated. Dose interruption, cycle delay, or dose reduction may be required for patients who develop grade 3 or 4 neutropenia.⁴

Patients should also be counseled to promptly report fever, infection symptoms, new or worsening cough, shortness of breath, or other respiratory symptoms. Palbociclib should be interrupted while suspected pneumonitis is evaluated and permanently discontinued in patients who develop severe interstitial lung disease or pneumonitis.⁴

Palbociclib is metabolized primarily through CYP3A. Strong CYP3A inhibitors can increase palbociclib exposure, whereas strong CYP3A inducers may reduce exposure and potentially compromise efficacy. Pharmacists should review prescription medications, over-the-counter products, supplements, and food interactions, including grapefruit and grapefruit juice, before treatment begins and throughout therapy.⁴

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. FDA. June 24, 2026. Accessed June 24, 2026.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-palbociclib-trastuzumab-or-without-pertuzumab-and-endocrine-therapy-maintenance

2. Palbociclib. National Cancer Institute. Updated February 10, 2015. Accessed June 24, 2026.https://www.cancer.gov/about-cancer/treatment/drugs/palbociclib

3. Randomized, open label, clinical study of palbociclib plus anti-HER2 therapy and endocrine therapy in HER2-positive, HR-positive metastatic breast cancer (PATINA). ClinicalTrials.gov identifier: NCT02947685. Accessed June 24, 2026. https://clinicaltrials.gov/study/NCT02947685

4. Pfizer’s IBRANCE in combination with standard-of-care therapies extends median progression-free survival by over 15 months in phase 3 PATINA study in patients with HR-positive, HER2-positive metastatic breast cancer. Pfizer. December 12, 2024. Accessed June 24, 2026. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-ibrancer-combination-standard-care-therapies