Palbociclib Plus Endocrine Therapy May Prolong Progression-Free Survival for Premenopausal Patients With HR-Positive, HER2-Negative Breast Cancer

According to extended follow-up results from the phase 2 Young-PEARL trial, palbociclib plus exemestane and ovarian function suppression prolonged progression-free survival compared to capecitabine among premenopausal patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer.

In this multicenter, open-label study, 174 premenopausal patients with HR-positive, HER2-negative metastatic breast cancer who experienced disease progression after prior lines of tamoxifen and were aromatase inhibitor-naive were enrolled into the modified intention-to-treat population. Patients were randomized on a 1-to-1 basis to receive either 125 mg of daily palbociclib on a 3-week-on, 1-week-off schedule plus 25 mg of daily exemestane and 3.75 mg of leuproelin on day 1 of each 28-day cycle (palbociclib arm, n = 90) or 1250 mg/m² of twice daily capecitabine on a 2-week-on, 1-week-off schedule (capecitabine arm, n = 84) until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and safety. 

At a median follow-up of 54 months, median PFS was 19.5 months in the palbociclib arm and 14 months in the capecitabine am (hazard ratio [HR] 0.74; 95% confidence interval [CI], 0.57 to 0.98; P = .036). Median OS was 54.8 months in the palbociclib arm and 57.8 months in the capecitabine arm (HR 1.02; 95% CI, 0.69 to 1.51; P = .92). Fifty-two patients died in the palbociclib arm and 48 patients died in the capecitabine arm. The most common grade ≥3 treatment-related adverse event observed was neutropenia. No treatment-related deaths occurred.

“Given the progression-free survival benefit, the upfront use of palbociclib plus endocrine therapy is the preferred option for premenopausal women, although a capecitabine-first strategy might be an alternative treatment strategy for maintaining overall survival in resource-limited settings,” concluded Dr Ahn et al. 

Source: 

Ahn HK, Kim JY, Lee KH, et al. Palbociclib plus endocrine therapy versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (Young-PEARL): Overall survival analysis of a randomised, open-label, phase 2 study. Lancet Oncol. Published online: February 17, 2025. doi: 10.1016/S1470-2045(25)00006-3