Palbociclib Extends Progression-Free Survival in HER2-Positive, Hormone Receptor-Positive Breast Cancer
A new era in the treatment of hormone receptor-positive (HR+) and HER2-positive (HER2+) advanced breast cancer is underway. The phase III PATINA trial, recently published in the New England Journal of Medicine, demonstrates that adding the CDK4/6 inhibitor palbociclib to standard maintenance therapy after initial chemotherapy significantly prolongs progression-free survival (PFS) in patients with this aggressive form of the disease.
Significant Improvement in Progression-Free Survival
With a median follow-up of over 53 months, the PATINA trial revealed that patients receiving palbociclib in combination with anti-HER2 therapy and endocrine therapy achieved a median PFS of 44.3 months, compared to 29.1 months for those treated with standard therapy alone. This translates to a 25% reduction in the risk of disease progression or death, a benefit observed consistently across all clinical subgroups analyzed.
A New Standard of Care?
“The PATINA study marks a before and after in the treatment of HER2-positive breast cancer with hormone receptors,” explains Dr. Eva Ciruelos, vice president of SOLTI and principal investigator of the study in Spain. “For the first time, a phase III trial demonstrates that a maintenance strategy can very significantly prolong the time to progression in patients who have responded or stabilized their disease after induction treatment.”
Understanding the PATINA Trial Design
The PATINA trial (AFT-38/NCT02947685) is a pivotal, open-label, international, phase III study. ClinicalTrials.gov identifies the trial as evaluating the efficacy and safety of palbociclib. The study’s design addresses a critical need in the treatment paradigm. Current standard of care for first-line treatment of HR+/HER2+ metastatic breast cancer typically involves chemotherapy combined with dual anti-HER2 blockade. While effective, optimizing the treatment phase after initial disease control remained a key area for improvement.
PATINA investigated whether adding palbociclib to maintenance treatment – following four to eight cycles of induction chemotherapy – could delay tumor progression. The results validate this approach, establishing maintenance therapy as a clinically impactful strategy.
Hormonal Pathway Dependence and Therapeutic Maintenance
“This study validates an idea that had been brewing for years in academic research,” says Dr. Alex Prat, a member of the study’s Steering Committee and director of the Clínic Barcelona Comprehensive Cancer Centre. “We knew that HER2+ tumors can change their biology after initial treatment and become more dependent on the hormonal pathway. PATINA shows that taking advantage of this moment with palbociclib has a clear benefit for patients.”
International Collaboration
The PATINA study involved extensive participation from hospital centers in Spain and Portugal, with a total of 23 active centers – 19 in Spain and 4 in Portugal. A total of 122 patients were included, with 113 recruited in Spain and 9 in Portugal, making Spain a major contributor to the trial internationally. The study was coordinated by SOLTI, with contributions from Dr. Santiago Escrivá and Dr. Xavier González.
Safety and Future Directions
The study found no new safety signals, and palbociclib’s tolerability profile was consistent with previous observations in HR+/HER2-negative breast cancer. This is particularly critical for maintenance treatment, where patient quality of life is paramount.
“The challenge now is how to integrate this strategy into real clinical practice, especially with the arrival of new induction therapies such as antibody-drug conjugates,” says Dr. Ciruelos. “But the message is clear: maintenance is here to stay and must be part of the approach to these patients.”
Approximately 10% of breast cancers are HR+/HER2+, a historically challenging subtype. The PATINA results offer the potential to transform the disease into a chronic condition for a growing number of patients, extending both survival and the time without disease progression or the need for further treatment lines.
“We are beginning to observe the light in a disease that a decade ago generated enormous fear,” concludes Dr. Prat. “The next step will be to continue intelligently combining the entire therapeutic arsenal available to further improve these results.”
The PATINA study was led by Alliance Foundation Trials, LLC (AFT) and principal investigator Dr. Otto Metzger, with collaboration from Pfizer. SOLTI coordinated the study in Spain and Portugal.