A Study of Palbociclib With Exemestane Plus GnRH Versus Capecitabine in Premenopausal Women With HR+ MBC

Summary

Despite recent advances for the treatment of post-menopausal hormone receptor-positive BC, in the last decade there was no major improvement of hormonal therapy specifically for premenopausal metastatic breast cancer. The median age of breast cancer is much younger, and the proportion of young breast cancer (YBC) patients (less than 40) including premenopausal women is much higher, in Asia, including Korea. Capecitabine, the comparator in this trial, is an orally-administered fluoropyrimidine derivative and has shown high efficacy and low toxicity in metastatic breast cancer patients. Palbociclib is a CDK4/6 inhibitors, in combination with endocrine therapy showed marked advance in hormone receptor-positive MBC in the post-menopausal setting. After a median follow-up of 16.5 months, preliminary results from Part 1 of this Phase 2 trial suggest that the combination of PD-0332991 with letrozole is superior to letrozole alone, and improved objective response and disease control rates (52% vs 32% and 76% vs 47%, respectively) in patients treated with the combination. These remarkable results may contribute to have much benefit with endocrine therapy for premenopausal women. Most importantly, recent PALOMA-3 trial revealed superior results of adding palbociclib to fulvestrant (median PFS 9.2 vs 3.8 months, P\<0.001). Based on these rational backgrounds, the purpose of this phase II study is to assess the safety and the clinical anti-tumor activity of exemestane plus goserelin acetate in combination with palbociclib vs capecitabine in premenopausal hormone receptor-positive advanced breast cancer patients

Timeline

Start

2016-06

Primary completion

2021-06

Completion

2021-06

Publications

• Ahn HK, Kim JY, Lee KH, Kim GM, Kang SY, Lee KS, Kim JH, Lee KE, Lee MH, Kim HJ, Kim HJ, Koh SJ, Park IH, Sohn J, Kim SB, Ahn JS, Kim S, Cho H, Jung KH, Im SA, Park YH; Korean Cancer Study Group (KCSG) Breast Cancer Committee. 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. 2025 Mar;26(3):343-354. doi: 10.1016/S1470-2045(25)00006-3. Epub 2025 Feb 17.
• Park YH, Kim TY, Kim GM, Kang SY, Park IH, Kim JH, Lee KE, Ahn HK, Lee MH, Kim HJ, Kim HJ, Lee JI, Koh SJ, Kim JY, Lee KH, Sohn J, Kim SB, Ahn JS, Im YH, Jung KH, Im SA; Korean Cancer Study Group (KCSG). Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2019 Dec;20(12):1750-1759. doi: 10.1016/S1470-2045(19)30565-0. Epub 2019 Oct 24.

Drugs

Indications