ASCEND：阿卡替尼对比伊布替尼联合利妥昔单抗或苯达莫司汀联合利妥昔单抗治疗复发或难治性慢性淋巴细胞白血病的 III 期随机试验。
ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia.
机构信息
Università Vita-Salute San Raffaele, Milano, Italy.
Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milano, Italy.
出版信息
J Clin Oncol. 2020 Sep 1;38(25):2849-2861. doi: 10.1200/JCO.19.03355. Epub 2020 May 27.
PURPOSE
Acalabrutinib, a highly selective, potent, Bruton tyrosine kinase inhibitor, was evaluated in this global, multicenter, randomized, open-label, phase III study in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).
METHODS
Eligible patients, aged ≥ 18 years with R/R CLL, were randomly assigned 1:1 centrally and stratified by del(17p) status, Eastern Cooperative Oncology Group performance status score, and number of prior lines of therapy. Patients received acalabrutinib monotherapy or investigator's choice (idelalisib plus rituximab [I-R] or bendamustine plus rituximab [B-R]). The primary end point was progression-free survival (PFS) assessed by an independent review committee (IRC) in the intent-to-treat population. Key secondary end points included IRC-assessed overall response rate, overall survival, and safety.
RESULTS
From February 21, 2017, to January 17, 2018, a total of 398 patients were assessed for eligibility; 310 patients were randomly assigned to acalabrutinib monotherapy (n = 155) or investigator's choice (n = 155; I-R, n = 119; B-R, n = 36). Patients had received a median of two prior therapies (range, 1-10). After a median follow-up of 16.1 months (range, 0.03-22.4 months), median PFS was significantly longer with acalabrutinib monotherapy (PFS not reached) compared with investigator's choice (16.5 months [95% CI, 14.0 to 17.1 months]; hazard ratio, 0.31 [95% CI, 0.20 to 0.49]; < .0001). Estimated 12-month PFS was 88% (95% CI, 81% to 92%) for acalabrutinib and 68% (95% CI, 59% to 75%) for investigator's choice. Serious adverse events occurred in 29% of patients (n = 44 of 154) treated with acalabrutinib monotherapy, 56% (n = 66 of 118) with I-R, and 26% (n = 9 of 35) with B-R. Deaths occurred in 10% (n = 15 of 154), 11% (n = 13 of 118), and 14% (n = 5 of 35) of patients receiving acalabrutinib monotherapy, I-R, and B-R, respectively.
CONCLUSION
Acalabrutinib significantly improved PFS compared with I-R or B-R and has an acceptable safety profile in patients with R/R CLL.
目的
阿卡鲁替尼是一种高度选择性、强效的布鲁顿酪氨酸激酶抑制剂，在复发/难治性（R/R）慢性淋巴细胞白血病（CLL）患者中进行的这项全球性、多中心、随机、开放标签、III 期研究中进行了评估。
方法
年龄≥18 岁的 R/R CLL 患者符合入选条件，按 1:1 比例随机分配，采用中央分组，并按 del(17p)状态、东部肿瘤协作组体力状态评分和既往治疗线数分层。患者接受阿卡鲁替尼单药治疗或研究者选择的治疗（idelalisib 联合利妥昔单抗[I-R]或苯达莫司汀联合利妥昔单抗[B-R]）。主要终点是无进展生存期（PFS），由独立审查委员会（IRC）在意向治疗人群中评估。关键次要终点包括 IRC 评估的总缓解率、总生存期和安全性。
结果
从 2017 年 2 月 21 日至 2018 年 1 月 17 日，共有 398 例患者接受了入选评估；310 例患者随机分配至阿卡鲁替尼单药治疗（n=155）或研究者选择的治疗（n=155；I-R，n=119；B-R，n=36）。患者中位接受过 2 线治疗（范围，1-10 线）。在中位随访 16.1 个月（范围，0.03-22.4 个月）后，与研究者选择的治疗相比，阿卡鲁替尼单药治疗的中位 PFS 显著延长（未达到 PFS）（16.5 个月[95%CI，14.0 至 17.1 个月]；风险比，0.31[95%CI，0.20 至 0.49]；<0.0001）。估计 12 个月时的 PFS 分别为 88%（95%CI，81%至 92%）和 68%（95%CI，59%至 75%）。阿卡鲁替尼单药治疗、I-R 和 B-R 组中分别有 29%（n=44）、56%（n=66）和 26%（n=9）的患者发生严重不良事件。10%（n=15）、11%（n=13）和 14%（n=5）的患者因严重不良事件而死亡，分别接受阿卡鲁替尼单药治疗、I-R 和 B-R。
结论
阿卡鲁替尼与 I-R 或 B-R 相比，显著改善了 PFS，在 R/R CLL 患者中具有可接受的安全性。
Zotero 插件