Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Cancer Res Treat. 2021 Jul;53(3):695-702. doi: 10.4143/crt.2020.1246. Epub 2020 Dec 17.
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.
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.
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.
This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2- MBC patients irrespective of tamoxifen sensitivity.
YoungPEARL（KCSG-BR15-10）试验表明，与卡培他滨相比，对于激素受体阳性/人表皮生长因子受体 2 阴性（HR+/HER2-）转移性乳腺癌（MBC）的绝经前患者，接受 palbociclib 联合依西美坦加卵巢功能抑制治疗具有显著的无进展生存期（PFS）获益。然而，由于大多数复发发生在辅助内分泌治疗（ET）早期，且仅使用他莫昔芬作为药物，因此接受他莫昔芬治疗的绝经前患者数量较少；因此，这些患者的数据有限。在此，我们根据 YoungPEARL 研究中他莫昔芬的敏感性进行了亚组分析。
患者按 1:1 随机接受 palbociclib+ET（口服依西美坦 25mg/天，连用 28 天，palbociclib 125mg/天，连用 21 天，加用每 4 周皮下注射亮丙瑞林 3.75mg）或化疗（卡培他滨 1250mg/m2，每日 2 次，连用 14 天，每 3 周 1 次）。他莫昔芬耐药定义为：辅助他莫昔芬期间复发、辅助他莫昔芬完成后 12 个月内复发或一线他莫昔芬治疗 6 个月内 MBC 进展。
共随机分配了 184 例患者，其中 178 例患者纳入改良意向治疗人群。在他莫昔芬敏感患者中观察到 palbociclib+ET 组的 PFS 改善（风险比，0.38；95%置信区间，0.12 至 1.19）。此外，与卡培他滨相比，palbociclib+ET 延长了他莫昔芬敏感（20.5 个月 vs. 12.6 个月）和他莫昔芬耐药（20.1 个月 vs. 14.5 个月）患者的中位 PFS。palbociclib+ET 在他莫昔芬敏感患者中显示出更高的客观缓解率、疾病控制率和临床获益率。
本探索性事后分析表明，无论他莫昔芬的敏感性如何，palbociclib+ET 都是 HR+/HER2-MBC 绝经前患者的一种有前途的治疗选择。
