FDA approves palbociclib combination for advanced HR-positive HER2-positive breast cancer

Today, Alliance Foundation Trials, LLC (AFT) was informed that the U.S. Food and Drug Administration has approved palbociclib in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for adult patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–positive (HER2+) locally advanced or metastatic breast cancer following induction treatment. This marks a major milestone and offers new hope for individuals living with this challenging subtype of advanced breast cancer.

The FDA approval is based on results from the pivotal phase III PATINA trial (AFT-38) that demonstrated that the addition of the CDK4/6 inhibitor palbociclib to standard first-line maintenance therapy significantly prolongs progression-free survival (PFS) demonstrating a 24% reduction in the risk of progression or death compared with standard therapy alone.

This approval reflects the culmination of years of collaborative research aimed at improving outcomes for patients with HR-positive, HER2-positive metastatic breast cancer. The PATINA trial demonstrated a significant and clinically meaningful delay in disease progression, and we are pleased that patients and physicians now will have access to a treatment option informed by these landmark phase III results."

Evanthia Galanis, MD, DSc, President of Alliance Foundation Trials and Group Chair of the Alliance for Clinical Trials in Oncology

Approximately 10% of all breast cancers are HR+, HER2+, sometimes referred to as double-positive or triple-positive breast cancer. Despite treatment advances, resistance to anti-HER2 and endocrine therapy remains a challenge, underscoring the need for new therapeutic strategies.

"PATINA answered an important clinical question and established that the addition of palbociclib to standard maintenance therapy can significantly extend progression-free survival in this patient population," said Otto Metzger, MD, Principal Investigator of PATINA and Associate Medical Director of International Strategic Initiatives at Dana-Farber Cancer Institute. "This approval translates those findings into a new treatment option for patients and provides clinicians with another tool to help manage a complex and challenging disease."

The PATINA (AFT-38) trial evaluated whether adding palbociclib to anti-HER2 therapy and endocrine therapy after four to eight cycles of induction chemotherapy could delay disease progression. The trial, which results were previously published in the New England Journal of Medicine and presented at the 2024 San Antonio Breast Cancer Symposium, found that patients receiving palbociclib experienced a meaningful improvement in median PFS, with no new safety signals.

"The AFT Statistics and Data Center coordinated a centralized clinical database for this international trial, enabling a timely final PFS analysis," noted Sumithra Mandrekar, PhD, faculty statistician and AFT SDC program director. From June 2017 through July 2021, the trial enrolled 518 patients across 109 clinical sites in the U.S., Europe, New Zealand, and Australia. Participants who had no prior treatment in the advanced setting beyond induction were randomly assigned to receive either palbociclib with anti-HER2 and endocrine therapy (n=261) or anti-HER2 and endocrine therapy alone (n=257). Findings demonstrated an extension of PFS of more than 15 months (median PFS increased from 29.1 to 44.3 months) with the addition of palbociclib to anti-HER2 and endocrine therapy in this patient population.

The PATINA (AFT-38) trial was funded by Pfizer Inc. and supported by an academic collaboration led by Alliance Foundation Trials, LLC as the global sponsor in partnership with Breast Cancer Trials (Australia and New Zealand), Fondazione Michelangelo (Italy), GBG (Germany), PrECOG (U.S.), SOLTI (Spain and Portugal), and Unicancer (France).