PATINA: 1L palbociclib combo extends PFS in HR+, HER2+ mBC

Addition of palbociclib to maintenance therapy yielded a median progression-free survival (mPFS) approaching 4 years, representing an effective first-line (1L) treatment for patients with hormone receptor–positive (HR+), HER2-positive (HER2+) metastatic breast cancer (mBC), according to the phase III PATINA trial.

The current standard 1L treatment for HR+, HER2+ mBC consists of induction chemotherapy, followed by maintenance therapy with dual HER2 blockade and endocrine therapy. It is hypothesized that the addition of palbociclib, a selective cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, to maintenance therapy may overcome resistance to both endocrine and HER2-directed therapies, thereby improving disease control and potential survival outcomes. [N Engl J Med 2026;394:451-462]

To test this hypothesis, researchers conducted the phase III, open-label, randomized PATINA trial at 123 sites in eight countries. A total of 518 patients with HR+, HER2+ mBC (median age, 53.4 years; female, 99.4 percent; postmenopausal, 61.8 percent) who did not have disease progression after 4–8 cycles of chemotherapy plus HER2-targeted therapy were randomized 1:1 to receive maintenance HER2-targeted and endocrine therapies with (n=261) or without palbociclib (standard therapy group; n=257).

PATINA: 1L mPFS approaching 4 years

After a median follow-up of 53.5 months, mPFS was significantly longer with palbociclib vs standard therapy (44.3 vs 29.1months; hazard ratio, 0.75; 95 percent confidence interval [CI], 0.59–0.96; two-sided p=0.02; stratified p=0.03).

“The achievement of mPFS beyond 44 months represents a meaningful clinical advance, and the median follow-up of 53.5 months provides mature and robust estimates of PFS,” wrote the researchers.

“We are seeing a 15.2-month improvement in mPFS — it’s more than a year of improvement with the addition of palbociclib,” pointed out the study’s principal investigator, Dr Otto Metzger of Harvard Medical School, Massachusetts, US.

Estimated PFS rates at 12, 24 and 48 months were 84.9, 65.2 and 46.5 percent in the palbociclib group, and 73.2, 55.3 and 38.3 percent in the standard therapy group, respectively.

ORR, OS & safety profile

Confirmed objective response rate was higher with palbociclib vs standard therapy (32.9 vs 24.8 percent).

At data cut-off, overall survival was not mature yet, with a hazard ratio of 0.86 (95 percent CI, 0.61–1.23).

Adverse events (AEs) of any grade occurred in all patients in the palbociclib group and in 94.4 percent of those in the standard therapy group. Grade ≥3 AEs in the palbociclib group were mainly neutropenia (60.5 and 2.0 percent), leukopenia (16.1 vs 0.8 percent), and diarrhoea (9.6 vs 1.2 percent). No treatment-related deaths were reported in either group.

Rationale for blocking CDK4/6 in 1L HER2+ BC Tx

“These results suggest that palbociclib overcomes resistance to anti-HER2 therapy and endocrine therapy,” said Metzger. “The data support the potential of this maintenance treatment to slow disease progression and improve clinical outcomes, potentially representing a new standard of care in the HR+, HER2+ mBC population.”

Although the use of HER2-directed antibody–drug conjugates may be warranted in selected high-risk patients, “the PATINA study provided definitive proof that there is benefit to targeting more than just the HER2 pathway in HER2+ BC,” commented Dr Sara Hurvitz of the University of Washington School of Medicine, Seattle, US. “We need the right treatment for the right patient. We will be moving away from a ‘one size fits all’ approach to HER2+ BC.”