Sustained PFS benefit in breast cancer with palbociclib + exemestane with ovarian function suppression

Treatment with palbociclib plus exemestane with ovarian function suppression does not appear to produce improvements in overall survival (OS), although it yields sustained increases in progression-free survival (PFS) as compared with capecitabine in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer, according to updated data from the phase II Young-PEARL study.

Young-PEARL was conducted at 14 institutions in South Korea and included 184 premenopausal women with histologically confirmed hormone receptor-positive, HER2-negative metastatic breast cancer that recurred or progressed during or after previous tamoxifen treatment. They had to be naïve to aromatase inhibitors and had an Eastern Cooperative Oncology Group performance status of 0–2. One previous line of chemotherapy was allowed in the metastatic setting.

The patients were randomly assigned to receive either oral palbociclib (125 mg per day on a 3-weeks-on, 1-week off schedule) plus oral exemestane (5 mg daily) with subcutaneous leuprorelin (3.75 mg on day 1 of each 28-day cycle) (n=92) or oral capecitabine (1,250 mg/m² twice a day on a 2-weeks-on, 1-week-off schedule) until disease progression or unacceptable toxicity.

PFS was the primary endpoint, while OS was the secondary endpoint. Analyses were performed in the modified intention-to-treat population (n=90 in the palbociclib plus endocrine therapy group, n=84 in the capecitabine group).

Over a median follow-up of 54.0 months, median PFS remained significantly higher with palbociclib plus endocrine therapy than with capecitabine (19.5 vs 14.0 months; hazard ratio, 0.74, 90 percent confidence interval, 0.57–0.98; p=0.036). More than half of the patients in the palbociclib plus endocrine therapy group (58 percent) and the capecitabine group (57 percent) died, with a median OS of 54.8 months and 57.8 months, respectively (HR, 1.02, 95 percent CI, 0.69–1.51; p=0.92).

Neutropenia was the most common grade 3 or worse adverse event, occurring in 64 percent of patients in the palbociclib plus endocrine therapy group vs 18 percent in the capecitabine group. No treatment-related deaths were reported.

Overall, the findings support the upfront use of palbociclib plus endocrine therapy as the preferred option for premenopausal women, although a capecitabine-first strategy could help maintain OS in resource-limited settings.