Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA.
Atlanta Cancer Care, Atlanta, GA.
Clin Breast Cancer. 2019 Jun;19(3):188-196. doi: 10.1016/j.clbc.2018.12.017. Epub 2019 Jan 3.
Increased signaling through growth factor receptor pathways, including HER2, plays a role in resistance to endocrine therapy (ET) in patients with hormone receptor (HR)-positive metastatic breast cancer (MBC). Inhibition of mechanistic target of rapamycin improves outcomes when used in addition to ET in patients with HR-positive MBC, who previously received ET. We hypothesized that the additional use of trastuzumab (T) or everolimus (E) could restore sensitivity to ET in patients with endocrine-resistant, HR-positive, HER2-negative MBC.
Patients with endocrine-resistant HR-positive, HER2-negative MBC continued the ET during which they had experienced disease progression, and were randomized to receive T or E. At disease progression, patients could continue the therapy they were receiving and have E or T used in addition.
Fifty-four patients were randomized to the additional use of E (n = 30) or T (n = 24) with existing ET. Progression-free survival (PFS) was 5.7 months, and 2.2 months, respectively, and clinical benefit rate at 24 weeks was 48% and 11% for patients receiving E or T, respectively. PFS was 4.5 months and 3.1 months for patients in whom E (n = 16) or T (n = 12) was used post progression, respectively. There were no new safety signals apart from 2 patients who had a decreased ejection fraction while receiving E with ET.
These results suggest that E, but not T, can potentially reverse resistance to ET in patients with endocrine-resistant HR-positive, HER2-negative MBC. Further, the additional use of E with an ET to which the cancer has already been exposed might offer the possibility of delaying time to use of chemotherapy.
生长因子受体通路（包括 HER2）信号的增强在激素受体（HR）阳性转移性乳腺癌（MBC）患者内分泌治疗（ET）耐药中发挥作用。在先前接受 ET 的 HR 阳性 MBC 患者中，使用雷帕霉素的机械靶点抑制剂（mTOR）联合 ET 可改善结局。我们假设在接受 ET 治疗的内分泌耐药性 HR 阳性、HER2 阴性 MBC 患者中，额外使用曲妥珠单抗（T）或依维莫司（E）可能恢复对 ET 的敏感性。
内分泌耐药性 HR 阳性、HER2 阴性 MBC 患者继续接受 ET，在此期间他们的疾病进展，随机接受 T 或 E 治疗。疾病进展时，患者可以继续接受他们正在接受的治疗，并额外使用 E 或 T。
54 例患者被随机分配至在现有 ET 基础上额外使用 E（n=30）或 T（n=24）。无进展生存期（PFS）分别为 5.7 个月和 2.2 个月，24 周时临床获益率分别为 48%和 11%，接受 E 或 T 的患者分别为 48%和 11%。E（n=16）或 T（n=12）治疗后进展的患者 PFS 分别为 4.5 个月和 3.1 个月。除 2 例患者在 ET 中接受 E 治疗时射血分数降低外，未出现新的安全信号。
这些结果表明，E 而不是 T，可能潜在地逆转内分泌耐药性 HR 阳性、HER2 阴性 MBC 患者对 ET 的耐药性。此外，在已经暴露于 ET 的癌症患者中额外使用 E 可能提供延迟使用化疗的可能性。
