Fudan University Shanghai Cancer Center, Shanghai, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
Target Oncol. 2019 Apr;14(2):149-158. doi: 10.1007/s11523-019-00630-y.
Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue inhibitor, was the first drug approved to treat R/R PTCL.
As the distribution of PTCL subtypes differs between populations and few patients in the pivotal trial of pralatrexate were Asian, this study investigated the safety and efficacy of pralatrexate as monotherapy in Chinese patients with R/R PTCL.
In this single-arm, open-label, multicenter study, 71 patients with R/R PTCL (median [range] 2 [1-14] prior systemic treatments) were recruited from 15 centers in China and received pralatrexate IV 30 mg/m/week for 6 weeks in 7-week cycles (with vitamin B/folate). The primary endpoint was objective response rate (ORR) per central review (null hypothesis: ORR < 15%).
The study's primary objective was met: ORR (95% CI) was 52% (40-64%) (p < 0.001) and responses were observed across pre-specified patient subgroups. Median (95% CI) duration of response was 8.7 (3.3-14.1) months and first response was observed in Cycle 1 for most (84%) patients. Median (95% CI) progression-free survival and overall survival was 4.8 (3.1-8.1) months and 18.0 (10.4-NA) months, respectively. The most common treatment-emergent adverse events were stomatitis (68% [Grade 3/4: 20%]), anemia (49% [Grade 3/4: 24%]) and alanine aminotransferase increase (41% [Grade 3/4: 4%]).
These results demonstrate that pralatrexate may represent a promising treatment option for Chinese patients with R/R PTCL. The ORR of 52% compared favorably with prior studies of pralatrexate in other populations and there were no unanticipated side effects.
ClinicalTrials.gov identifier: NCT03349333.
外周 T 细胞淋巴瘤（PTCL）预后较差，尤其是在复发/难治（R/R）患者中。培拉曲塞是一种叶酸类似物抑制剂，是首个获批用于治疗 R/R PTCL 的药物。
由于 PTCL 亚型在不同人群中的分布不同，且在培拉曲塞的关键试验中接受治疗的亚洲患者较少，因此本研究旨在评估培拉曲塞单药治疗中国 R/R PTCL 患者的安全性和疗效。
这是一项在中国 15 家中心开展的单臂、开放标签、多中心研究，共纳入 71 例 R/R PTCL 患者（中位[范围]2[1-14]线既往全身治疗），接受培拉曲塞 IV 30mg/m/周，每 6 周为一个周期，共 7 周（联合维生素 B/叶酸）。主要终点为中心评估的客观缓解率（ORR）（无效假设：ORR<15%）。
研究达到了主要终点：ORR（95%CI）为 52%（40%-64%）（p<0.001），且在各预设患者亚组中均观察到应答。中位（95%CI）缓解持续时间为 8.7（3.3-14.1）个月，大多数（84%）患者在第 1 周期观察到首次缓解。中位（95%CI）无进展生存期和总生存期分别为 4.8（3.1-8.1）个月和 18.0（10.4-NR）个月。最常见的治疗相关不良事件为口腔炎（68%[3/4 级：20%]）、贫血（49%[3/4 级：24%]）和丙氨酸氨基转移酶升高（41%[3/4 级：4%]）。
这些结果表明，培拉曲塞可能成为中国 R/R PTCL 患者的一种有前景的治疗选择。52%的 ORR 与培拉曲塞在其他人群中的既往研究相比结果较好，且未观察到意外的副作用。
ClinicalTrials.gov 标识符：NCT03349333。
