Department of Neuro-Oncology (M.A., M.H., V.P.); Department of Biostatistics (K.H.), The University of Texas MD Anderson Cancer Center, Houston, Texas.
Neuro Oncol. 2014 Jun;16(6):823-8. doi: 10.1093/neuonc/nou021. Epub 2014 Mar 3.
Patients with recurrent glioblastoma benefiting from bevacizumab are often treated indefinitely due to concerns regarding rebound tumor recurrence upon discontinuation. However, treatment is discontinued for reasons other than disease progression in a subset of these patients, the characteristics and outcomes of which are poorly defined.
Of 342 adults with recurrent glioblastoma in our database treated with bevacizumab, 82 received treatment for ≥ 6 months; of these, bevacizumab was discontinued for reasons other than tumor progression in 18 patients (Bev-D) and for disease progression in the remainder (Bev-S). The impact of discontinuation on outcome was assessed with discontinuation as a time-dependent covariate in a Cox hazards model for progression-free survival.
There was no difference in hazard rates for progression between Bev-D and Bev-S groups; the adjusted hazard ratio for progression using discontinuation as a time-dependent covariate was 0.91 (95% CI:0.47, 1.78). The median PFS after bevacizumab-discontinuation was 27 weeks (95% CI:15-NR). At progression, a higher proportion of Bev-D patients had local progression compared with the Bev-S patients. Salvage therapy in Bev-D patients yielded a PFS-26 weeks of 47% (95% CI:23%-94%) with a median PFS of 23 weeks (95% CI:12-NR), vs. 5% (95% CI: 1%-21%) and 9 weeks (95% CI: 6-11) in Bev-S patients (HR:0.3;CI, 0.1-0.6) (P = .0007).
Bevacizumab discontinuation unrelated to disease progression does not appear to cause rebound recurrence or worsen PFS in patients who benefit from bevacizumab. Additionally, Bev-D patients had an improved response to salvage therapy, findings which provide a strong basis for a prospective study.
由于担心停止使用贝伐珠单抗后肿瘤会复发，接受贝伐珠单抗治疗后病情复发的胶质母细胞瘤患者通常会无限期接受治疗。然而，由于其他原因而不是疾病进展，这些患者中有一部分会停止治疗，其特征和结果尚不清楚。
在我们的数据库中，有 342 名复发性胶质母细胞瘤成人患者接受了贝伐珠单抗治疗，其中 82 名患者接受了至少 6 个月的治疗；在这些患者中，有 18 名（Bev-D 组）由于肿瘤进展以外的原因停止了治疗，其余患者（Bev-S 组）则因疾病进展而停止了治疗。使用贝伐珠单抗停药作为无进展生存期的时间依赖协变量，在 Cox 风险模型中评估停药对结果的影响。
Bev-D 组和 Bev-S 组的进展风险率没有差异；使用贝伐珠单抗停药作为时间依赖协变量时，进展的调整后的风险比为 0.91（95%CI：0.47，1.78）。贝伐珠单抗停药后中位无进展生存期为 27 周（95%CI：15-NR）。在进展时，Bev-D 组患者中局部进展的比例高于 Bev-S 组。Bev-D 组患者的挽救性治疗的中位无进展生存期为 23 周（95%CI：12-NR），26 周无进展生存期的比例为 47%（95%CI：23%-94%），而 Bev-S 组患者的中位无进展生存期为 9 周（95%CI：6-11），26 周无进展生存期的比例为 5%（95%CI：1%-21%）（HR：0.3；CI，0.1-0.6）（P =.0007）。
对于从贝伐珠单抗治疗中获益的患者，贝伐珠单抗停药与疾病进展无关，似乎不会导致肿瘤复发或无进展生存期恶化。此外，Bev-D 组患者对挽救性治疗的反应有所改善，这为前瞻性研究提供了有力的依据。
