Implications of Tamoxifen Resistance in Palbociclib Efficacy for Patients with Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Subgroup Analyses of KCSG-BR15-10 (YoungPEARL)

Jiyun Lee; Seock-Ah Im; Gun Min Kim; Kyung Hae Jung; Seok Yun Kang; In Hae Park; Jee Hyun Kim; Hee Kyung Ahn; Yeon Hee Park

doi:10.4143/crt.2020.1246

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Implications of Tamoxifen Resistance in Palbociclib Efficacy for Patients with Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Subgroup Analyses of KCSG-BR15-10 (YoungPEARL)

Authors: Jiyun Lee ; Seock-Ah Im ; Gun Min Kim ; Kyung Hae Jung ; Seok Yun Kang ; In Hae Park ; Jee Hyun Kim ; Hee Kyung Ahn ; Yeon Hee Park

Citation: CANCER RESEARCH AND TREATMENT, Vol.53(3) : 695-702, 2021-07

Journal Title: CANCER RESEARCH AND TREATMENT

ISSN: 1598-2998

Issue Date: 2021-07

MeSH: Adult ; Androstadienes / pharmacology ; Androstadienes / therapeutic use ; Antineoplastic Agents, Hormonal / pharmacology ; Antineoplastic Agents, Hormonal / therapeutic use ; Antineoplastic Combined Chemotherapy Protocols / pharmacology* ; Antineoplastic Combined Chemotherapy Protocols / therapeutic use ; Breast Neoplasms / mortality ; Breast Neoplasms / pathology ; Breast Neoplasms / therapy* ; Chemotherapy, Adjuvant / methods ; Clinical Trials, Phase II as Topic ; Female ; Humans ; Mastectomy ; Middle Aged ; Multicenter Studies as Topic ; Neoplasm Recurrence, Local / mortality ; Neoplasm Recurrence, Local / pathology ; Neoplasm Recurrence, Local / therapy* ; Piperazines / pharmacology* ; Piperazines / therapeutic use ; Progression-Free Survival ; Protein Kinase Inhibitors / pharmacology ; Protein Kinase Inhibitors / therapeutic use ; Pyridines / pharmacology* ; Pyridines / therapeutic use ; Randomized Controlled Trials as Topic ; Receptor, ErbB-2 / analysis ; Receptors, Estrogen / analysis ; Receptors, Estrogen / metabolism ; Receptors, Progesterone / analysis ; Receptors, Progesterone / metabolism ; Tamoxifen / pharmacology* ; Tamoxifen / therapeutic use

Keywords: Breast neoplasms ; CDK4/6 inhibitor ; Endocrine therapy ; Palbociclib ; Tamoxifen

Abstract: Purpose: YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study.

Materials and methods: Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC.

Results: In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients.

Conclusion: This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2- MBC patients irrespective of tamoxifen sensitivity.