Azim Hamdy A, Saleh Mariam A, Essam Eldin Passant, Abdelhafeez Ahmed A M, Hassan Mohamed, Kassem Loay
Clinical Oncology Department, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt.
Anatomic Pathology Department, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt.
J Chemother. 2025 Apr;37(2):159-167. doi: 10.1080/1120009X.2024.2342741. Epub 2024 May 20.
First line endocrine therapy is the gold standard for advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Adding CDK4/6 inhibitors has improved progression free survival. Metronomic Capecitabine has proven to be safe to combine with endocrine therapy with promising efficacy. We conducted a phase II randomized, open label, single centre clinical trial on patients with metastatic ER positive and HER 2 negative breast cancer. Eligible patients were randomized (1:1) to arm A: metronomic dose of capecitabine (500 mg/m BID) combined with letrozole (2.5 mg OD) or arm B: letrozole single agent. The primary endpoint was progression free survival. The study was terminated early due to poor accrual and 60 eligible patients out of the planned 204 were randomized. This clinical trial is registered on ClinicalTrials.gov (MD-127-2019, NCT04571437). Between February 2019 and April 2022, 60 patients were randomized. This is the first report of the study, after a median follow-up of 18.6 months. The median age at diagnosis was 47 years with only 41.7% of patients post-menopausal. Half of our patients had bone-only disease, 45% had visceral metastasis (liver and lung) and 63% presented with endocrine sensitive disease. The estimated median PFS for the whole population was 16.2 months. Median PFS for capecitabine arm was 17.7 months versus 14.6 months for letrozole alone ( = 0.078). Overall response rate was 70% for capecitabine/letrozole arm and 56.6% for letrozole only. Clinical benefit rate was 90% in the capecitabine/letrozole arm versus 73.3% in the letrozole arm. Overall survival data is still immature after this short follow up duration. Adverse event assessment showed acceptable all grade and high grade toxicity profile consistent with the established adverse events of both capecitabine and letrozole. Anaemia (28.3%) and hand & foot syndrome (43.8%) were significantly more common in the capecitabine/letrozole arm. Capecitabine combined with letrozole have showed a trend towards improvement in progression free survival with potential more benefit to certain sub-groups and the combination showed acceptable safety profile consistent with the established known safety profile of both letrozole and capecitabine.
一线内分泌治疗是晚期雌激素受体阳性、人表皮生长因子受体2阴性乳腺癌的金标准。添加CDK4/6抑制剂可改善无进展生存期。已证实小剂量持续服用卡培他滨与内分泌治疗联合使用安全且疗效可期。我们对转移性雌激素受体阳性和人表皮生长因子受体2阴性乳腺癌患者进行了一项II期随机、开放标签、单中心临床试验。符合条件的患者被随机分组（1:1）至A组：小剂量持续服用卡培他滨（500mg/m²，每日两次）联合来曲唑（2.5mg，每日一次）或B组：来曲唑单药治疗。主要终点是无进展生存期。由于入组情况不佳，该研究提前终止，计划入组的204例患者中有60例符合条件的患者被随机分组。该临床试验已在ClinicalTrials.gov上注册（MD - 127 - 2019，NCT04571437）。在2019年2月至2022年4月期间，60例患者被随机分组。这是该研究的首次报告，中位随访时间为18.6个月。诊断时的中位年龄为47岁，仅41.7%的患者为绝经后患者。我们一半的患者仅患有骨转移，45%有内脏转移（肝脏和肺），63%表现为内分泌敏感型疾病。整个人群的估计中位无进展生存期为16.2个月。卡培他滨组的中位无进展生存期为17.7个月，而来曲唑单药组为14.6个月（P = 0.078）。卡培他滨/来曲唑组的总体缓解率为70%，来曲唑单药组为56.6%。卡培他滨/来曲唑组的临床获益率为90%，来曲唑组为73.3%。在如此短的随访期后，总生存数据仍不成熟。不良事件评估显示，所有级别和高级别毒性特征均可接受，与卡培他滨和来曲唑既定的不良事件一致。贫血（28.3%）和手足综合征（43.8%）在卡培他滨/来曲唑组中明显更常见。卡培他滨联合来曲唑显示出无进展生存期有改善的趋势，对某些亚组可能有更多益处，并且该联合用药显示出可接受的安全性特征，与来曲唑和卡培他滨既定的已知安全性特征一致。
