Kanner Andrew A, Wong Eric T, Villano John L, Ram Zvi
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Beth Israel Deaconess Medical Center, Boston, MA.
Semin Oncol. 2014 Oct;41 Suppl 6:S25-34. doi: 10.1053/j.seminoncol.2014.09.008. Epub 2014 Sep 16.
We performed a treatment-based analysis of data from the pivotal phase III trial of the NovoTTF-100A System™ versus best physician's choice (BPC) chemotherapy in patients with recurrent glioblastoma multiforme (GBM), with particular focus on efficacy in patients using NovoTTF Therapy as intended. Median overall survival (OS) was compared for recurrent GBM patients receiving at least one full cycle of treatment with NovoTTF-100A System or BPC chemotherapy (modified intention-to-treat [mITT] population) in the recently reported phase III trial. The relationship between NovoTTF-100A System compliance and OS was evaluated in the ITT population. Kaplan-Meier analyses examined treatment-related differences in OS for various patient subgroups. Median OS was significantly higher in patients receiving≥1 course of NovoTTF Therapy versus BPC (7.7 v 5.9 months; hazard ratio, 0.69; 95% confidence interval [CI], 0.52-0.91; P = .0093). Median OS was also significantly higher in patients receiving NovoTTF Therapy with a maximal monthly compliance rate≥75% (≥18 hours daily) versus those with a<75% compliance rate (7.7 v 4.5 months; P = .042), and Kaplan-Meier analysis demonstrated a significant trend for improved median OS with higher compliance (P = .039). Additional post hoc analysis showed significantly higher median OS with NovoTTF Therapy than with BPC for patients with prior low-grade glioma, tumor size≥18 cm(2), Karnofsky performance status≥80, and those who had previously failed bevacizumab therapy. When used as intended in mITT patients with recurrent GBM, NovoTTF Therapy provides an OS benefit compared with chemotherapy in patients with recurrent GBM. This contrasts with the equivalent efficacy reported previously based on analysis of all randomized ITT subjects, including many who did not receive a full cycle of treatment. Higher NovoTTF Therapy compliance corresponds with greater survival benefit in the present study.
我们对NovoTTF - 100A系统™与最佳医生选择（BPC）化疗用于复发性多形性胶质母细胞瘤（GBM）患者的关键III期试验数据进行了基于治疗的分析，特别关注按预期使用NovoTTF疗法的患者的疗效。在最近报告的III期试验中，比较了接受至少一个完整周期NovoTTF - 100A系统或BPC化疗的复发性GBM患者（改良意向性治疗[mITT]人群）的中位总生存期（OS）。在ITT人群中评估了NovoTTF - 100A系统依从性与OS之间的关系。Kaplan - Meier分析检查了不同患者亚组中OS与治疗相关的差异。接受≥1疗程NovoTTF疗法的患者的中位OS显著高于接受BPC化疗的患者（7.7个月对5.9个月；风险比，0.69；95%置信区间[CI]，0.52 - 0.91；P = 0.0093）。每月最大依从率≥75%（每天≥18小时）接受NovoTTF疗法的患者的中位OS也显著高于依从率<75%的患者（7.7个月对4.5个月；P = 0.042），并且Kaplan - Meier分析显示随着依从性提高，中位OS有显著改善趋势（P = 0.039）。额外的事后分析显示，对于既往患有低级别胶质瘤、肿瘤大小≥18 cm²、卡诺夫斯基功能状态≥80以及既往贝伐单抗治疗失败的患者，NovoTTF疗法的中位OS显著高于BPC化疗。在复发性GBM的mITT患者中按预期使用时，与化疗相比，NovoTTF疗法为复发性GBM患者提供了OS益处。这与之前基于对所有随机ITT受试者（包括许多未接受完整周期治疗的受试者）的分析报告的等效疗效形成对比。在本研究中，更高的NovoTTF疗法依从性对应着更大的生存益处。
