Palbociclib Combination Therapy Improves Outcomes for HR-positive, HER2-positive Metastatic Breast Cancer

Palbociclib (Ibrance; Pzifer) in combination with standard-of-care anti-HER2 and endocrine therapy (ET) in the first-line maintenance setting achieved statistically significant improvements in progression-free survival (PFS) in patients with hormone receptor (HR)-positive, human epidermal receptor factor 2 (HER2)-positive metastatic breast cancer (MBC). The data from the phase 3 AFT-38 PATINA trial (NCT02947685) were presented at the 2024 San Antonio Breast Cancer Symposium.¹

Wooden blocks spelling HER2+ | Image Credit: © AnnJane - stock.adobe.com

HR-positive, HER2-positive breast cancer (BC) is aggressive and can be challenging to treat, accounting for about 10% of all BC cases. Despite treatment advancements, some patients develop resistance to anti-HER2 and endocrine therapies, underscoring the need for therapeutic alternatives.²

“PATINA is the first large phase 3 study to show the benefit of CDK4/6 inhibition in HR-positive, HER2-positive metastatic breast cancer,” Otto Metzger, MD, principal investigator of the trial for Alliance Foundation Trials and Medical Oncologist at the Dana-Farber Cancer Institute, said in a press release. “These results support the potential of this maintenance treatment to slow disease progression and improve clinical outcomes in this patient population.”²

Palbociclib is an oral CDK4/6 inhibitor that was approved by the FDA in 2017 for treatment of patients with HR-positive, HER2-negative MBC as initial therapy combined with an aromatase inhibitor in postmenopausal women or with fulvestrant in patients who experienced disease progression after ET. In the randomized, open-label, phase 3 AFT-38 PATINA trial, palbociclib demonstrated safety and efficacy in first-line maintenance therapy after induction chemotherapy for patients with HR-positive, HER2-positive MBC.^2,3

The trial assessed palbociclib in combination with anti-HER2 therapy (trastuzumab or trastuzumab) plus pertuzumab, and ET compared with anti-HER2 therapy and ET alone as a first-line maintenance therapy. Patients were randomly assigned to receive the palbociclib combination treatment (n=261) or anti-HER2 therapy and ET alone (n=257). Primary and secondary end points included PFS and overall survival (OS), respectively.^2,4

According to the study results, patients in the palbociclib arm achieved a median PFS of 44.3 months (95% CI: 32.4-60.9) compared with 29.1 months (95% CI: 23.3-38.6) for patients treated with anti-HER2 therapy and ET [HR: 0.74 (95% CI, 0.58-0.94); unstratified 1-sided p= 0.0074]. At the time of analysis, OS data were immature, and median OS was not reached in the palbociclib arm. The 5-year survival rates were 74.3% and 69.8% in the palbociclib and control arms, respectively.^2,4

The most common adverse events (AEs) were grade 3 neutropenia (63.2%), grade 2 and 3 fatigue (28.3%), stomatitis (21.4%), and diarrhea (37.5%). AEs less than or equal to grade 4 were similar across study arms (12.3% vs 8.9% for palbociclib vs control; P = .21). The investigators reported no treatment-related deaths in either study arm.^2,4

“PATINA is the first phase III trial to show that the addition of the CDK4/6 inhibitor palbociclib was of benefit as first-line maintenance therapy in HR-positive, HER2-positive metastatic breast cancer in combination with anti-HER2 and endocrine therapy,” Metzger, MD, study principal investigator and assistant professor of medicine at Harvard Medical School and a medical oncologist at the Dana-Farber Cancer Institute, said in an article published by The ASCO Post. “These results suggest that palbociclib overcomes resistance to anti-HER2 therapy and endocrine therapy. The data support the potential of this maintenance treatment to slow disease progression and improve clinical outcomes in this patient population. This may represent a new standard of care for patients diagnosed with HR-positive, HER2-positive metastatic breast cancer.”⁴

REFERENCES

1. Randomized, open label, clinical study of the targeted therapy, palbociclib, to treat metastatic breast cancer (PATINA). Updated September 19, 2024. Accessed Junary 8, 2025. https://clinicaltrials.gov/study/NCT02947685

2. 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+, HER2+ metastatic breast cancer. Pfizer. December 12, 2024. Accessed January 8, 2025. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-ibrancer-combination-standard-care-therapies

3. Palbociclib (IBRANCE). FDA. March 31, 2017. Accessed Junary 8, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/palbociclib-ibrance

4. Addition of palbociclib to standard therapy in metastatic hormone receptor–positive, HER2-positive breast cancer. The ASCO Post. January 7, 2025. Accessed January 8, 2025. https://ascopost.com/news/january-2025/addition-of-palbociclib-to-standard-therapy-in-metastatic-hormone-receptor-positive-her2-positive-breast-cancer/