阿帕鲁胺与非转移性去势抵抗性前列腺癌的总生存期。
Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer.
机构信息
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montréal, QC, Canada.
出版信息
Ann Oncol. 2019 Nov 1;30(11):1813-1820. doi: 10.1093/annonc/mdz397.
BACKGROUND
In the SPARTAN study, compared with placebo, apalutamide added to ongoing androgen deprivation therapy significantly prolonged metastasis-free survival (MFS) and time to symptomatic progression in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). Overall survival (OS) results at the first interim analysis (IA1) were immature, with 104 of 427 (24%) events required for planned final OS analysis. Here, we report the results of a second pre-specified interim analysis (IA2).
METHODS
One thousand two hundred and seven patients with nmCRPC were randomized 2 : 1 to apalutamide (240 mg daily) or placebo. The primary end point of the study was MFS. Subsequent therapy for metastatic CRPC was permitted. When the primary end point was met, the study was unblinded. Patients receiving placebo who had not yet developed metastases were offered open-label apalutamide. At IA2, pre-specified analysis of OS was undertaken, using a group-sequential testing procedure with O'Brien-Fleming-type alpha spending function. Safety and second progression-free survival (PFS2) were assessed.
RESULTS
Median follow-up was 41 months. With 285 (67% of required) OS events, apalutamide was associated with an improved OS compared with placebo (HR 0.75; 95% CI 0.59-0.96; P = 0.0197), although the P-value did not cross the pre-specified O'Brien-Fleming boundary of 0.0121. Apalutamide improved PFS2 (HR 0.55; 95% CI 0.45-0.68). At IA2, 69% of placebo-treated and 40% of apalutamide-treated patients had received subsequent life-prolonging therapy for metastatic CRPC. No new safety signals were observed.
CONCLUSION
In patients with nmCRPC, apalutamide was associated with a 25% reduction in risk of death compared with placebo. This OS benefit was observed despite crossover of placebo-treated patients and higher rates of subsequent life-prolonging therapy for the placebo group.
背景
在 SPARTAN 研究中，与安慰剂相比，阿帕鲁胺联合持续雄激素剥夺治疗显著延长了高危非转移性去势抵抗性前列腺癌（nmCRPC）患者的无转移生存期（MFS）和症状进展时间。在第一次中期分析（IA1）时，总体生存（OS）结果不成熟，计划最终 OS 分析需要 427 例中有 104 例（24%）事件。在此，我们报告第二次预定中期分析（IA2）的结果。
方法
1207 例 nmCRPC 患者按 2：1 随机分配接受阿帕鲁胺（240mg 每日）或安慰剂治疗。该研究的主要终点为 MFS。随后允许转移性 CRPC 接受治疗。当主要终点达到时，研究被揭盲。尚未发生转移的安慰剂组患者可接受开放标签阿帕鲁胺治疗。在 IA2 时，采用 O'Brien-Fleming 型 alpha 分配函数的分组序贯检验程序，对 OS 进行了预先设定的分析。评估了安全性和第二次无进展生存期（PFS2）。
结果
中位随访时间为 41 个月。在发生 285 例（需要的 67%）OS 事件后，与安慰剂相比，阿帕鲁胺可改善 OS（HR 0.75；95%CI 0.59-0.96；P=0.0197），尽管 P 值未越过预先设定的 O'Brien-Fleming 界限 0.0121。阿帕鲁胺改善了 PFS2（HR 0.55；95%CI 0.45-0.68）。在 IA2 时，安慰剂组 69%和阿帕鲁胺组 40%的患者接受了转移性 CRPC 的后续延长生命治疗。未观察到新的安全性信号。
结论
在 nmCRPC 患者中，与安慰剂相比，阿帕鲁胺可使死亡风险降低 25%。尽管安慰剂组的患者交叉接受了阿帕鲁胺治疗，且该组随后的延长生命治疗率较高，但仍观察到 OS 获益。
Zotero 插件