Vahdat Linda T, Schmid Peter, Forero-Torres Andres, Blackwell Kimberly, Telli Melinda L, Melisko Michelle, Möbus Volker, Cortes Javier, Montero Alberto J, Ma Cynthia, Nanda Rita, Wright Gail S, He Yi, Hawthorne Thomas, Bagley Rebecca G, Halim Abdel-Baset, Turner Christopher D, Yardley Denise A
Weill Cornell Medicine, New York, NY, USA.
Center for Experimental Cancer Medicine, Barts Cancer Institute, London, UK.
NPJ Breast Cancer. 2021 May 20;7(1):57. doi: 10.1038/s41523-021-00244-6.
The METRIC study (NCT#0199733) explored a novel antibody-drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m PO daily d1-14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.
METRIC研究（NCT编号：0199733）探索了一种新型抗体药物偶联物——戈沙妥珠单抗（GV），其靶向在约40%的三阴性乳腺癌（TNBC）患者中过表达且与预后不良相关的糖蛋白非转移性黑色素瘤蛋白B（gpNMB）。该研究是一项随机、开放标签的2b期研究，评估了在gpNMB过表达的TNBC中，GV与卡培他滨相比的无进展生存期（PFS）。既往接受过蒽环类和紫杉类治疗的患者按2:1随机分组，接受GV（1.88mg/kg静脉注射，每21天一次）或卡培他滨（2500mg/m²口服，每日一次，第1 - 14天，每21天一个周期）。主要终点是根据独立、盲态的中心评估得出的RECIST 1.1标准的PFS。共有327例患者被随机分配至GV组（213例接受治疗）或卡培他滨组（92例接受治疗）。GV组的中位PFS为2.9个月，卡培他滨组为2.8个月。GV组最常见的≥3级毒性反应为中性粒细胞减少、皮疹和白细胞减少，卡培他滨组为疲劳、腹泻和手足红斑性感觉异常。该研究未达到优于卡培他滨改善PFS的主要终点，也未显示出相对于卡培他滨有相对风险/获益的改善。
