曲妥珠单抗联合聚乙二醇化脂质体阿霉素治疗转移性乳腺癌患者。希腊合作肿瘤学组（HeCOG）的II期研究及生物标志物评估

Trastuzumab combined with pegylated liposomal doxorubicin in patients with metastatic breast cancer. phase II Study of the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation.

作者信息

Christodoulou Christos, Kostopoulos Ioannis, Kalofonos Haralabos P, Lianos Evangelos, Bobos Mattheos, Briasoulis Evangelos, Gogas Helen, Razis Evangelia, Skarlos Dimosthenis V, Fountzilas George

机构信息

Second Department of Medical Oncology, Henry Dunant Hospital, Athens, Greece.

出版信息

Oncology. 2009;76(4):275-85. doi: 10.1159/000207504. Epub 2009 Mar 5.

DOI:10.1159/000207504

PMID:19262067

Abstract

OBJECTIVE

Combination of trastuzumab and anthracyclines in metastatic breast cancer (MBC) is precluded due to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is the least cardiotoxic among the anthracyclines. We performed a phase II study of trastuzumab and PLD with biomarker evaluation.

METHODS

Patients with MBC and HER2 overexpression, assessed as 3+ at local laboratories, received trastuzumab 8 mg/kg as loading dose followed by 6 mg/kg in combination with PLD 30 mg/m(2), both given every 3 weeks. To be eligible, patients should have received first-line chemotherapy for MBC or should have relapsed within a year of adjuvant taxane. Tumor tissue blocks were collected for central review and exploratory biomarker evaluation. Left-ventricular ejection fraction (LVEF) was closely monitored by cardiac ultrasound.

RESULTS

Among 37 patients, an overall response rate of 22% was observed with a progression-free survival (PFS) of 6.5 months (0.8-31.1, 95% CI 2.7-10.3) and a survival of 18.7 months (1.6-40.8, 95% CI 3.7-33.7). No decline in LVEF was noticed. Overexpression of mTOR and TOP2A gene alterations were associated with better PFS. PTEN gene deletion was associated with resistance to treatment.

CONCLUSION

Trastuzumab combined with PLD every 3 weeks is feasible, effective and safe in HER2-positive patients.

摘要

目的

由于存在心脏毒性，转移性乳腺癌（MBC）中曲妥珠单抗与蒽环类药物联合使用受到限制。聚乙二醇化脂质体阿霉素（PLD）是蒽环类药物中心脏毒性最小的。我们开展了一项曲妥珠单抗与PLD联合使用并进行生物标志物评估的II期研究。

方法

在当地实验室评估为HER2过表达（3+）的MBC患者，先接受8mg/kg的曲妥珠单抗负荷剂量，随后接受6mg/kg，同时联合30mg/m²的PLD，均每3周给药一次。符合条件的患者应接受过MBC的一线化疗，或在辅助性紫杉烷治疗后一年内复发。收集肿瘤组织块进行中心审查和探索性生物标志物评估。通过心脏超声密切监测左心室射血分数（LVEF）。

结果

37例患者中，总缓解率为22%，无进展生存期（PFS）为6.5个月（0.8 - 31.1，95%CI 2.7 - 10.3），总生存期为18.7个月（1.6 - 40.8，95%CI 3.7 - 33.7）。未观察到LVEF下降。mTOR过表达和TOP2A基因改变与更好的PFS相关。PTEN基因缺失与治疗耐药相关。