FDA Approves Palbociclib Plus Trastuzumab, With/Without Pertuzumab, and ET as Maintenance in HR+, HER2+ Metastatic 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 adult patients with hormone receptor–positive, HER2-positive locally advanced or metastatic breast cancer following induction treatment.¹

The regulatory decision was supported by data from the phase 3 PATINA trial (NCT02947685). Findings from the trial showed that palbociclib with trastuzumab, with or without pertuzumab, and endocrine therapy produced a significant investigator-assessed progression-free survival (PFS) benefit compared with trastuzumab, with or without pertuzumab, and endocrine therapy alone (HR, 0.76; 95% CI, 0.59-0.97; 1-sided P = .0134). The median PFS values could not be adequately described because of censoring. At the time of the PFS analysis, the overall survival (OS) data were not mature.

The palbociclib prescribing information includes warnings and precautions for neutropenia, interstitial lung disease/pneumonitis, and embryo-fetal toxicity. The recommended palbociclib dosage is 125 mg orally once daily for 21 consecutive days, followed by 7 days off treatment to comprise a complete cycle of 28 days.

How was PATINA designed?

PATINA was a randomized, open-label trial that enrolled 518 patients with hormone receptor–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, for their advanced disease. Additional key eligibility criteria included being at least 18 years of age, having an ECOG performance status of 0 or 1, and having adequate baseline laboratory values.²

Eligible patients were randomly assigned 1:1 to receive either palbociclib with trastuzumab, with or without pertuzumab, and endocrine therapy (fulvestrant [Faslodex] or an aromatase inhibitor [anastrozole, letrozole, or exemestane]); or trastuzumab, with or without pertuzumab, and endocrine therapy alone.^1,2 Palbociclib was given orally at a starting dose of 125 mg once per day for 21 days followed by 7 days off to complete the 28-day cycle; dose reductions to 100 mg and/or 75 mg were permitted.² Dosing of trastuzumab was based on a loading dose of 8 mg/kg administered every 3 weeks or a maintenance dose of 6mg/kg every 3 weeks; the loading dose was administered on day 1 of cycle 1. Pertuzumab was given at a loading dose of 840 mg, followed by a maintenance dose of 420 mg every 3 weeks; if a patient was within 5 weeks of receiving the loading dose at day 1, cycle 1, they were permitted to start with a maintenance dose of 420 mg.

Patients underwent treatment until disease progression or unacceptable toxicity.

The primary end point was investigator-assessed PFS per RECIST 1.1 criteria. Secondary end points included OS, objective response rate (ORR), duration of response (DOR), clinical benefit rate, safety, patient-reported outcomes, and incidence of central nervous system metastases. Pharmacokinetic measures were assessed as explortatory end points.

What prior data have been reported from PATINA?

Earlier data from PATINA published in the New England Journal of Medicine demonstrated that the estimated 12-, 24-, and 48-month PFS rates in the investigational arm (n = 261) were 84.9%, 65.2%, and 46.5%, respectively.³ In the control arm (n = 257), these respective rates were 73.2%, 55.3%, and 38.3%. The confirmed ORRs in the investigational and control arms were 32.9% (95% CI, 26.9%-39.4%) and 24.8% (95% CI, 19.3%-30.0%), respectively. The respective median durations of confirmed response were 44.9 months (95% CI, 27.1-51.6) and 30.8 months (95% CI, 26.0-not evaluable).

In terms of safety, patients in the investigational (n = 261) and control (n = 248) arms experienced any-grade adverse effects (AEs) at respective rates of 100% and 94.4%. The most common any-grade AEs in the palbociclib arm included neutropenia (77.8%), diarrhea (70.5%), and fatigue (53.6%). The most common any-grade AEs in the control arm included arthralgia (48.0%), fatigue (39.9%), and diarrhea (37.5%).

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. Randomized, open label, clinical study of the targeted therapy, palbociclib, to treat metastatic breast cancer (PATINA). ClinicalTrials.gov. Updated February 12, 2026. Accessed June 24, 2026. https://clinicaltrials.gov/study/NCT02947685
3. Metzger O, Mandrekar S, Goel S, et al. Palbociclib for hormone-receptor-positive, HER2-positive advanced breast cancer. N Engl J Med. 2026;394(5):451-462. doi:10.1056/NEJMoa2511218