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)

• Published in: Cancer research and treatment Vol. 53; no. 3; pp. 695 - 702
• Main Authors: Lee, Jiyun, Im, Seock-Ah, Kim, Gun Min, Jung, Kyung Hae, Kang, Seok Yun, Park, In Hae, Kim, Jee Hyun, Ahn, Hee Kyung, Park, Yeon Hee
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Cancer Association 01.07.2021; 대한암학회
• Subjects: 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; Original; 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; 의학일반; Endocrine therapy; Breast neoplasms; Tamoxifen; Palbociclib; CDK4/6 inhibitor
• ISSN: 1598-2998; 2005-9256; 2005-9256
• DOI: 10.4143/crt.2020.1246

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.