Palbociclib Boosts Progression-Free Survival in HER2-Positive Metastatic Breast Cancer: Study

A new study published in The New England Journal of Medicine found HER2-positive metastatic breast cancer to show that the addition of palbociclib to standard maintenance therapy significantly prolongs the time patients live without disease progression.

For this subtype of metastatic breast cancer, the current first-line standard of care involves dual anti-HER2 therapy combined with chemotherapy, followed by maintenance treatment using HER2-targeted agents and endocrine therapy. However, resistance to both endocrine and HER2-directed therapies remains a major clinical challenge. Palbociclib, a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), has shown promise on earlier laboratory and clinical studies. This trial set out to test whether that promise would translate into meaningful long-term benefits.

This study enrolled patients whose disease had not progressed after completing four to 8 cycles of chemotherapy plus HER2-targeted therapy. A total of 518 patients were randomized evenly into a group receiving maintenance HER2-targeted and endocrine therapies plus palbociclib, while the control group received maintenance therapy alone. The main outcome measured was progression-free survival, with additional evaluations of tumor response, clinical benefit, safety, and overall survival.

After a median follow-up of 53.5 months, the results clearly favored the palbociclib-containing regimen. Patients receiving palbociclib experienced a median progression-free survival of 44.3 months, when compared to 29.1 months in the standard-therapy group. This translated into a 25% reduction in the risk of disease progression or death. The difference was statistically significant, reinforcing the robustness of the finding.

The results explained about the secondary outcomes, like objective response rates and clinical benefit, along with safety data. In particular, adverse events are broken down by severity, which highlighted the higher incidence of grade 3 and 4 toxic effects in the palbociclib group.

Safety findings revealed an important trade-off. While the addition of palbociclib improved disease control, it was associated with increased toxicity. Nearly 80% of patients in the palbociclib group experienced grade 3 adverse events, and 10% experienced grade 4 events, most commonly neutropenia.

In contrast, severe adverse events were substantially less frequent in the standard-therapy group. Overall, the study concludes that adding palbociclib to maintenance anti-HER2 and endocrine therapy offers a meaningful progression-free survival benefit, albeit with increased side effects.

Source:

Metzger, O., Mandrekar, S., Goel, S., Gligorov, J., Lim, E., Ciruelos, E., Loibl, S., Dockter, T., Gonzàlez Farré, X., Francis, P. A., Lynce, F., Lanzillotti, J., DuFrane, C., Wall, A., Strand, C., Krop, I., Vaz-Luis, I., Tripathy, D., Loi, S., … Carey, L. A. (2026). Palbociclib for hormone-receptor-positive, HER2-positive advanced breast cancer. The New England Journal of Medicine, 394(5), 451–462. https://doi.org/10.1056/NEJMoa2511218