In an overall survival analysis of a South Korean phase II trial (Young-PEARL) reported in The Lancet Oncology, Ahn et al found no benefit with palbociclib plus exemestane and leuprorelin vs capecitabine in premenopausal women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer. The primary analysis of the trial showed a significant progression-free survival benefit with palbociclib plus endocrine therapy.
Study Details
In the multicenter open-label trial, 174 aromatase inhibitor–naive patients (modified intention-to-treat population) with disease that recurred or progressed during or after previous tamoxifen treatment were randomly assigned between June 2016 and December 2018 to receive palbociclib plus endocrine therapy (n = 90) or capecitabine at 1,250 mg/m² twice daily on a 2-weeks-on/1-week-off schedule (n = 84) until disease progression or unacceptable toxicity. Palbociclib-endocrine therapy consisted of palbociclib at 125 mg/d on a 3-weeks-on, 1-week off schedule plus exemestane at 25 mg daily with leuprorelin at 3.75 mg subcutaneously on day 1 of each 28-day cycle. Patients could have received one previous line of chemotherapy in the metastatic setting.
Key Findings
At data cutoff (end of February 2024), median follow-up was 54.0 months (interquartile range = 34.1–74.4 months).
Death occurred in 58% of the palbociclib-endocrine therapy group and 57% of the capecitabine group. Median overall survival was 54.8 months (95% confidence interval [CI] = 48.9–77.1 months) with palbociclib plus endocrine therapy vs 57.8 months (95% CI = 46.3–89.2 months) with capecitabine group (hazard ratio [HR] = 1.02, 95% CI = 0.69–1.51, P = .92).
With extended follow-up, median progression-free survival was 19.5 months (90% CI = 14.3–22.2 months) with palbociclib plus endocrine therapy vs 14.0 months (95% CI = 11.7–18.7 months) with capecitabine (HR = 0.74, 90% CI = 0.57–0.98, P = .036).
Overall, the most common grade ≥ 3 adverse event was neutropenia (64% vs 18%). No treatment-related deaths were observed.
The investigators concluded: “With extended follow-up, palbociclib plus exemestane with ovarian function suppression continued to show a significant benefit in progression-free survival compared with capecitabine in premenopausal patients with hormone receptor–positive, HER2-negative metastatic breast cancer who had been previously treated with tamoxifen; however, no improvement in overall survival was seen. 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.”
Yeon Hee Park, MD, of the Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the Ministry of Health & Welfare, South Korea, and Pfizer. For full disclosures of the study authors, visit thelancet.com.
