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Abstract：
UNASSIGNED: For patients with hormone receptor-positive HER2-negeative metastatic breast cancer (HR+HER2- MBC), switching to another cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) or targeted drugs with different mechanism are considerable treatment strategies post-CDK4/6i. However, no clinical data has been reported on which of the two strategies is more effective. In order to explore optimal treatment option post-CDK4/6i, we performed a retrospective comparative cohort study to evaluate the efficacy and safety of abemaciclib-based therapy versus tucidinostat-based therapy after progression on palbociclib.
UNASSIGNED: We identified patients with HR+HER2- MBC who had received abemaciclib-based therapy or tucidinostat-based therapy after progression on palbociclib from the database of Chinese Society of Clinical Oncology Breast Cancer (CSCO BC). Baseline characteristics, efficacy and safety information of treatments were derived from seven research centers\' medical records. The primary endpoint was progression-free survival (PFS), the secondary endpoints were clinical benefit rate (CBR), PFS according to PIK3CA gene type, and safety.
UNASSIGNED: Between April 1st 2020 and June 30th 2022, a total of 149 patients were included, of whom 73 patients received abemaciclib plus endocrine therapy (ET), and 76 patients received tucidinostat plus ET. The majority of patients had visceral disease (124/149, 83.2%) and ≥3 metastatic organs (76/149, 51.0%), one third (48/149, 32.2%) had previously been treated ≥3 lines of ET at baseline in MBC setting. CBR was 38.4% (28/73) in abemaciclib group and 17.1% (13/76) in tucidinostat group (P=0.004). There was significant difference in PFS between abemaciclib group and tucidinostat group in both the whole population (5.0 vs. 2.0 months; hazard ratio =0.44; 95% CI: 0.31-0.64; P<0.001) and propensity score matched population. PIK3CA mutations occurred in 44.20% of patients who had undergone multigene sequencing. PIK3CA-mutant showed a negative effect on PFS of abemaciclib-based therapy. Neutropenia was the most common adverse event in both groups for any grade and grades 3-4. Common non-hematological toxicity occurred in abemaciclib group was diarrhea (27.4%), and were increased aspartate aminotransferase (AST) (26.3%), nausea (25.0%), vomiting (11.8%) and hypokalemia (13.2%) in tucidinostat group.
UNASSIGNED: Our study suggests superiority of abemaciclib-based therapy over tucidinostat-based therapy in patients progressed on palbociclib, which merits further assessment in larger and prospective trials.
UNASSIGNED: We identified patients with HR+HER2- MBC who had received abemaciclib-based therapy or tucidinostat-based therapy after progression on palbociclib from the database of Chinese Society of Clinical Oncology Breast Cancer (CSCO BC). Baseline characteristics, efficacy and safety information of treatments were derived from seven research centers\' medical records. The primary endpoint was progression-free survival (PFS), the secondary endpoints were clinical benefit rate (CBR), PFS according to PIK3CA gene type, and safety.
UNASSIGNED: Between April 1st 2020 and June 30th 2022, a total of 149 patients were included, of whom 73 patients received abemaciclib plus endocrine therapy (ET), and 76 patients received tucidinostat plus ET. The majority of patients had visceral disease (124/149, 83.2%) and ≥3 metastatic organs (76/149, 51.0%), one third (48/149, 32.2%) had previously been treated ≥3 lines of ET at baseline in MBC setting. CBR was 38.4% (28/73) in abemaciclib group and 17.1% (13/76) in tucidinostat group (P=0.004). There was significant difference in PFS between abemaciclib group and tucidinostat group in both the whole population (5.0 vs. 2.0 months; hazard ratio =0.44; 95% CI: 0.31-0.64; P<0.001) and propensity score matched population. PIK3CA mutations occurred in 44.20% of patients who had undergone multigene sequencing. PIK3CA-mutant showed a negative effect on PFS of abemaciclib-based therapy. Neutropenia was the most common adverse event in both groups for any grade and grades 3-4. Common non-hematological toxicity occurred in abemaciclib group was diarrhea (27.4%), and were increased aspartate aminotransferase (AST) (26.3%), nausea (25.0%), vomiting (11.8%) and hypokalemia (13.2%) in tucidinostat group.
UNASSIGNED: Our study suggests superiority of abemaciclib-based therapy over tucidinostat-based therapy in patients progressed on palbociclib, which merits further assessment in larger and prospective trials.
摘要：
■对于激素受体阳性HER2阳性转移性乳腺癌（HR+HER2-MBC）患者，转换为另一种细胞周期蛋白依赖性激酶4/6抑制剂(CDK4/6i)或具有不同机制的靶向药物是CDK4/6i后相当重要的治疗策略.然而,尚无关于两种策略中哪一种更有效的临床数据报道.为了探索CDK4/6i后的最佳治疗选择，我们进行了一项回顾性对比队列研究,以评估基于abemaciclib的治疗与基于tucidinostat的治疗在palbociclib进展后的疗效和安全性.
■我们从中国临床肿瘤学会乳腺癌（CSCOBC）数据库中确定了HR+HER2-MBC患者在palbociclib进展后接受了基于abemaciclib的治疗或基于tucidinostat的治疗。基线特征，治疗的有效性和安全性信息来自七个研究中心的医疗记录。主要终点是无进展生存期（PFS），次要终点是临床获益率（CBR），PFS根据PIK3CA基因类型，和安全。
■在2020年4月1日至2022年6月30日期间，共包括149名患者，其中73例患者接受了abemaciclib加内分泌治疗（ET），76例患者接受了tucidinostat联合ET治疗。大多数患者有内脏疾病（124/149，83.2%）和≥3个转移器官（76/149，51.0%），1/3(48/149,32.2%)以前在MBC设置中接受过基线≥3行ET治疗.abemaciclib组为38.4%(28/73),tucidinostat组为17.1%(13/76)(P=0.004)。在整个人群中，abemaciclib组和tucidinostat组的PFS均存在显着差异（5.0vs.2.0个月；风险比=0.44；95％CI：0.31-0.64；P<0.001）和倾向评分匹配的人群。在接受多基因测序的患者中，PIK3CA突变发生率为44.20%。PIK3CA突变体对基于abemaciclib的治疗的PFS显示出负面影响。对于任何级别和3-4级，中性粒细胞减少症是两组中最常见的不良事件。abemaciclib组常见的非血液学毒性为腹泻(27.4%),天冬氨酸转氨酶（AST）增加（26.3%），恶心（25.0%），tucidinostat组的呕吐（11.8％）和低钾血症（13.2％）。
■我们的研究表明，在palbociclib进展的患者中，基于abemaciclib的治疗优于基于tucidinostat的治疗，这值得在更大和前瞻性试验中进一步评估。
■我们从中国临床肿瘤学会乳腺癌（CSCOBC）数据库中确定了HR+HER2-MBC患者在palbociclib进展后接受了基于abemaciclib的治疗或基于tucidinostat的治疗。基线特征，治疗的有效性和安全性信息来自七个研究中心的医疗记录。主要终点是无进展生存期（PFS），次要终点是临床获益率（CBR），PFS根据PIK3CA基因类型，和安全。
■在2020年4月1日至2022年6月30日期间，共包括149名患者，其中73例患者接受了abemaciclib加内分泌治疗（ET），76例患者接受了tucidinostat联合ET治疗。大多数患者有内脏疾病（124/149，83.2%）和≥3个转移器官（76/149，51.0%），1/3(48/149,32.2%)以前在MBC设置中接受过基线≥3行ET治疗.abemaciclib组为38.4%(28/73),tucidinostat组为17.1%(13/76)(P=0.004)。在整个人群中，abemaciclib组和tucidinostat组的PFS均存在显着差异（5.0vs.2.0个月；风险比=0.44；95％CI：0.31-0.64；P<0.001）和倾向评分匹配的人群。在接受多基因测序的患者中，PIK3CA突变发生率为44.20%。PIK3CA突变体对基于abemaciclib的治疗的PFS显示出负面影响。对于任何级别和3-4级，中性粒细胞减少症是两组中最常见的不良事件。abemaciclib组常见的非血液学毒性为腹泻(27.4%),天冬氨酸转氨酶（AST）增加（26.3%），恶心（25.0%），tucidinostat组的呕吐（11.8％）和低钾血症（13.2％）。
■我们的研究表明，在palbociclib进展的患者中，基于abemaciclib的治疗优于基于tucidinostat的治疗，这值得在更大和前瞻性试验中进一步评估。
