Palbociclib Maintenance Extends PFS in HR+/HER2+ Advanced Breast Cancer

Results from the phase 3 PATINA trial (NCT02947685) published in the New England Journal of Medicine showed that the addition of palbociclib (Ibrance) to maintenance anti-HER2 and endocrine therapies significantly extended progression-free survival (PFS) for patients with hormone receptor–positive, HER2-positive advanced breast cancer.¹

PATINA Trial Results

At a median follow-up of 53.5 months, patients in the palbociclib group experienced a median PFS of 44.3 months (95% CI, 32.4-56.8) compared with 29.1 months (95% CI, 23.3-38.6) in the standard therapy group. This represented a significant reduction in the hazard for disease progression or death (HR, 0.75; 95% CI, 0.59-0.96; 2-sided P = .02). Estimated PFS rates at 48 months were 46.5% for the palbociclib group and 38.3% for the standard therapy group.

Secondary efficacy end points also favored the palbociclib combination. The confirmed overall response rate (ORR)—excluding patients with a complete response to induction—was 32.9% (95% CI, 26.9%-39.4%) in the palbociclib group vs 24.8% (95% CI, 19.3%-30.0%) in the standard therapy group. The median duration of confirmed response was 44.9 months (95% CI, 27.1-51.6) with palbociclib and 30.8 months (95% CI, 26.0-nonevaluable [NE]) with standard therapy. The clinical benefit rate was 88.9% (95% CI, 84.4%-92.4%) among patients receiving palbociclib compared with 80.9% (95% CI, 75.6%-85.6%) for those receiving standard therapy. Overall survival (OS) data remained immature at the time of the final PFS analysis, with 60 deaths in the palbociclib group and 63 in the standard therapy group (HR, 0.86; 95% CI, 0.61-1.23).

“This publication in the New England Journal of Medicine underscores the importance of these findings for the global breast cancer community,” Otto Metzger, MD, associate medical director, International Strategic Initiatives, and physician at Dana-Farber Cancer Institute; assistant professor of medicine at Harvard Medical School; and principal investigator of PATINA, said in the press release.² “The ability to meaningfully extend [PFS] with a well-tolerated regimen offers new hope for individuals living with this challenging subtype of metastatic breast cancer.”

PATINA Trial Details

The PATINA trial enrolled patients who had completed 4 to 8 cycles of induction therapy consisting of trastuzumab (Herceptin) and pertuzumab (Perjeta) plus a taxane. Patients were randomly assigned in a 1:1 ratio to receive maintenance anti-HER2 and endocrine therapies with or without palbociclib. Palbociclib was administered orally at 125 mg daily for 21 days followed by 7 days off in 28-day cycles. Endocrine therapy included either an aromatase inhibitor or fulvestrant (Faslodex). Randomization was stratified by response to induction therapy, previous neoadjuvant or adjuvant anti-HER2 therapy, type of endocrine therapy, and single or dual HER2 blockade.

The trial randomly assigned 518 patients: 261 to the palbociclib group and 257 to the standard therapy group. The median age was 53.4 years, and 99.4% of patients were female. Postmenopausal patients comprised 61.8% of the population. Baseline characteristics indicated that 54.4% of patients had de novo metastatic disease. Visceral metastases were present in 73.6% of patients, and 3.9% had asymptomatic central nervous system metastases at diagnosis. Most patients (94.0%) received dual anti-HER2 therapy, and 90.7% received an aromatase inhibitor as their maintenance endocrine therapy.

The primary end point was investigator-assessed PFS, defined as the time from randomization to documented disease progression or death. Secondary end points included confirmed ORR, OS, clinical benefit rate, and safety.

The international, open-label, randomized study conducted at 123 sites in 8 countries sought to address potential resistance to standard treatments by concurrently inhibiting HER2, the estrogen receptor, and the cyclin D1–CDK4/6 axis. This maintenance strategy followed standard first-line induction chemotherapy plus HER2-targeted therapy for patients who had not experienced disease progression.

What Safety Results Occurred in the PATINA Trial?

Adverse events (AEs) of any grade occurred in 100% of the palbociclib group and 94.4% of the standard therapy group. Grade 3 AEs were significantly more frequent with the addition of palbociclib (79.7% vs 30.6%), primarily due to hematologic toxicities. Grade 3 neutropenia occurred in 55.9% of the palbociclib group vs 2.0% of the standard therapy group, and grade 4 neutropenia was reported in 4.6% and 0%, respectively. Two patients in the palbociclib group experienced febrile neutropenia.

Non-hematologic toxicities also increased with palbociclib. Grade 2 or higher fatigue was reported in 22.2% of the palbociclib group vs 12.9% of the standard therapy group. Diarrhea of any grade was more common with palbociclib (grade 2, 27.6% vs 10.9%; grade 3, 9.6% vs 1.2%). Palbociclib dose reductions occurred in 57.7% of patients, with a median time to first reduction of 3.2 months. AEs led to the discontinuation of palbociclib in 18.0% of patients. Serious AEs occurred in 28.7% of those in the palbociclib group compared with 21.8% in the standard therapy group. No treatment-related deaths were reported.

References

1. 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
2. Addition of CDK 4/6 inhibitor benefits patients with HR+, HER2+ metastatic breast cancer, new study shows. News release. Dana-Farber Cancer Institute. January 29, 2026. Accessed January 29, 2026. https://tinyurl.com/dvu4sj2b