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Abstract：
BACKGROUND: Cyclin-dependent kinase (CDK) 4/6 inhibitor plus endocrine therapy (ET) become standard-of-care for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, the optimal therapeutic paradigm after progression on CDK4/6 inhibitor remains unclear. This study aimed to evaluate the efficacy and safety of abemaciclib with switching ET versus chemotherapy after progression on prior palbociclib-based ET in Chinese patients with HR+/HER2- MBC.
METHODS: From 414 consecutive patients with HR+/HER2- MBC who had been treated with palbociclib plus ET from September 2018 to May 2022 in Peking University Cancer Hospital, we identified 80 patients who received abemaciclib plus switching ET or chemotherapy after progression on palbociclib, matched for age, original stage at diagnosis, disease-free interval, and tumor burden at 1:1 ratio. The primary endpoint was progression-free survival (PFS) compared using the Kaplan-Meier method. A Cox proportional hazard model was performed to identify clinical factors associated with PFS in the abemaciclib group.
RESULTS: The median PFS was 6.0 months (95% confidence interval [CI]: 3.94-8.06) in abemaciclib group and 4.0 months (95% CI, 2.52-5.49) in chemotherapy group (p = 0.667). And, there was no difference in median PFS between the sequential and nonsequential arm (6.0 vs. 6.0 months) in the abemaciclib group though fewer lines of prior systemic therapy and longer PFS from prior palbociclib in the sequential arm. However, patients with prior palbociclib as the first-line therapy had a significantly longer median PFS versus prior palbociclib as ≥2nd-line therapy (11.0 vs. 5.0 months, p = 0.043). Based on multivariable analysis, ER+/PR+ was an independent factor associated with longer PFS. There was no significant difference in overall survival between the abemaciclib and chemotherapy groups (p = 0.069).
CONCLUSIONS: Our findings indicate that abemaciclib plus switching ET might be one of feasible treatment options for Chinese patients with HR+/HER2- MBC after progression on prior palbociclib-based therapy in addition to chemotherapy.
METHODS: From 414 consecutive patients with HR+/HER2- MBC who had been treated with palbociclib plus ET from September 2018 to May 2022 in Peking University Cancer Hospital, we identified 80 patients who received abemaciclib plus switching ET or chemotherapy after progression on palbociclib, matched for age, original stage at diagnosis, disease-free interval, and tumor burden at 1:1 ratio. The primary endpoint was progression-free survival (PFS) compared using the Kaplan-Meier method. A Cox proportional hazard model was performed to identify clinical factors associated with PFS in the abemaciclib group.
RESULTS: The median PFS was 6.0 months (95% confidence interval [CI]: 3.94-8.06) in abemaciclib group and 4.0 months (95% CI, 2.52-5.49) in chemotherapy group (p = 0.667). And, there was no difference in median PFS between the sequential and nonsequential arm (6.0 vs. 6.0 months) in the abemaciclib group though fewer lines of prior systemic therapy and longer PFS from prior palbociclib in the sequential arm. However, patients with prior palbociclib as the first-line therapy had a significantly longer median PFS versus prior palbociclib as ≥2nd-line therapy (11.0 vs. 5.0 months, p = 0.043). Based on multivariable analysis, ER+/PR+ was an independent factor associated with longer PFS. There was no significant difference in overall survival between the abemaciclib and chemotherapy groups (p = 0.069).
CONCLUSIONS: Our findings indicate that abemaciclib plus switching ET might be one of feasible treatment options for Chinese patients with HR+/HER2- MBC after progression on prior palbociclib-based therapy in addition to chemotherapy.
摘要：
背景：细胞周期蛋白依赖性激酶（CDK）4/6抑制剂加内分泌治疗（ET）成为激素受体阳性患者的标准治疗方法，人表皮生长因子受体-2阴性（HR+/HER2-）转移性乳腺癌（MBC）。然而,CDK4/6抑制剂进展后的最佳治疗模式仍不清楚.这项研究旨在评估在中国HR/HER2-MBC患者中，在先前基于palbociclib的ET进展后，abemaciclib转换ET与化疗的疗效和安全性。
方法：自2018年9月至2022年5月在北京大学肿瘤医院接受帕博西尼联合ET治疗的414例连续HR+/HER2-MBC患者，我们确定了80例患者在palbociclib进展后接受了abemaciclib加转换ET或化疗，年龄相匹配，最初的诊断阶段，无病间隔，肿瘤负荷为1:1。主要终点是使用Kaplan-Meier方法比较的无进展生存期（PFS）。在abemaciclib组中进行Cox比例风险模型以确定与PFS相关的临床因素。
结果：abemaciclib组的中位PFS为6.0个月（95％置信区间[CI]：3.94-8.06），化疗组为4.0个月（95％CI，2.52-5.49）（p=0.667）。And,序贯组和非序贯组之间的中位PFS没有差异(6.0vs.6.0个月）在abemaciclib组中，尽管在序贯组中，先前的全身治疗路线较少，而先前的palbociclib的PFS较长。然而,先前palbociclib作为一线治疗的患者的中位PFS明显长于先前palbociclib作为≥二线治疗的患者（11.0vs.5.0个月,p=0.043)。基于多变量分析，ER+/PR+是延长PFS的独立因素。abemaciclib和化疗组之间的总生存期没有显着差异（p=0.069）。
结论：我们的研究结果表明，abemaciclib加转换ET可能是中国HR+/HER2-MBC患者进展后的可行治疗选择之一，除了化疗外，还使用基于palbociclib的治疗。
方法：自2018年9月至2022年5月在北京大学肿瘤医院接受帕博西尼联合ET治疗的414例连续HR+/HER2-MBC患者，我们确定了80例患者在palbociclib进展后接受了abemaciclib加转换ET或化疗，年龄相匹配，最初的诊断阶段，无病间隔，肿瘤负荷为1:1。主要终点是使用Kaplan-Meier方法比较的无进展生存期（PFS）。在abemaciclib组中进行Cox比例风险模型以确定与PFS相关的临床因素。
结果：abemaciclib组的中位PFS为6.0个月（95％置信区间[CI]：3.94-8.06），化疗组为4.0个月（95％CI，2.52-5.49）（p=0.667）。And,序贯组和非序贯组之间的中位PFS没有差异(6.0vs.6.0个月）在abemaciclib组中，尽管在序贯组中，先前的全身治疗路线较少，而先前的palbociclib的PFS较长。然而,先前palbociclib作为一线治疗的患者的中位PFS明显长于先前palbociclib作为≥二线治疗的患者（11.0vs.5.0个月,p=0.043)。基于多变量分析，ER+/PR+是延长PFS的独立因素。abemaciclib和化疗组之间的总生存期没有显着差异（p=0.069）。
结论：我们的研究结果表明，abemaciclib加转换ET可能是中国HR+/HER2-MBC患者进展后的可行治疗选择之一，除了化疗外，还使用基于palbociclib的治疗。
