在对激素受体阳性(HR+)患者进行abemaciclib测试的临床试验中,HER2阴性(HER2-)晚期乳腺癌,腹泻是一种非常常见的不良事件(发生在大约85%的患者中,任何等级)。尽管如此,由于使用了基于洛哌丁胺的有效支持疗法,这种毒性导致一小部分患者(约2%)停用abemaciclib.我们的目的是确定在现实世界试验中abemaciclib引起的腹泻的发病率是否高于临床试验中报道的发病率。病人被高度挑选,并评估在这种情况下标准支持治疗的成功率。我们做了一个回顾,观察,单中心研究包括2019年7月至2021年5月在我们机构接受abemaciclib和内分泌治疗的39例HR+/HER2-晚期乳腺癌患者。总的来说,任何级别的腹泻发生在36例患者中(92%),其中6人(17%)腹泻≥3级。在30名患者(77%)中,腹泻与其他不良事件有关,包括疲劳(33%),中性粒细胞减少症(33%),呕吐(28%),腹痛(20%),和肝毒性(13%)。26例患者(72%)接受了基于洛哌丁胺的支持治疗。Abemaciclib剂量减少了12例患者(31%)由于腹泻,4例患者(10%)永久停止治疗.在58%的患者(15/26)中,腹泻可通过支持性治疗得到有效治疗,不需要减少abemaciclib剂量和/或停药.在我们的现实分析中,与临床试验数据相比,我们观察到与abemaciclib相关的腹泻发生率更高,以及由于胃肠道毒性而导致的永久性治疗中断率较高。更好地实施基于指南的支持性护理可以帮助管理这种毒性。
In clinical trials testing
abemaciclib in patients with hormone-receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer, diarrhea is a very common adverse event (occurring in approximately 85% of patients, any grade). Nonetheless, this toxicity leads to
abemaciclib discontinuation in a small proportion of patients (approximately 2%) thanks to the use of effective loperamide-based supportive therapy. We aimed to determine whether the incidence of
abemaciclib-induced diarrhea in real-world trials was higher than the one reported in clinical trials, where patients are highly selected, and to evaluate the success rate of standard supportive care in this setting. We conducted a retrospective, observational, monocentric study including 39 consecutive patients with HR+/HER2- advanced breast cancer treated with abemaciclib and endocrine therapy at our institution from July 2019 to May 2021. Overall, diarrhea of any grade occurred in 36 patients (92%), of whom 6 (17%) had diarrhea of grade ≥3. In 30 patients (77%), diarrhea was associated with other adverse events, including fatigue (33%), neutropenia (33%), emesis (28%), abdominal pain (20%), and hepatotoxicity (13%). Loperamide-based supportive therapy was administered to 26 patients (72%). Abemaciclib dose was reduced in 12 patients (31%) due to diarrhea, and treatment was permanently discontinued in 4 patients (10%). In 58% of patients (15/26), diarrhea was effectively managed with supportive care and did not require abemaciclib dose reduction and/or discontinuation. In our real-world analysis, we observed a higher incidence of diarrhea related to
abemaciclib compared to data from clinical trials, and a higher rate of permanent treatment discontinuation due to gastrointestinal toxicity. Better implementation of
guideline-based supportive care could help to manage this toxicity.