Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Department of Chemotherapy, Anhui Provincial Hospital, Hefei, People's Republic of China.
J Thorac Oncol. 2021 Aug;16(8):1403-1414. doi: 10.1016/j.jtho.2021.04.001. Epub 2021 Apr 26.
ZL-2306-005 is a randomized, double-blind, multicenter phase 3 study evaluating the efficacy and safety of niraparib, a poly(adenosine diphosphate-ribose) polymerase inhibitor, as first-line maintenance therapy in Chinese patients with platinum-responsive, extensive-stage SCLC (ES-SCLC).
Patients with complete response (CR) or partial response (PR) to standardized, platinum-based first-line chemotherapy were randomized 2:1 to receive niraparib or placebo (300 mg [baseline body weight ≥ 77 kg, platelet count ≥ 150,000/μL] or 200 mg) once daily until progression or unacceptable toxicity. Primary end points were progression-free survival (PFS) (blinded independent central review) and overall survival (sample size planned: 591 patients). Secondary end points included investigator-evaluated PFS and safety.
ZL-2306-005 was terminated early owing to ES-SCLC treatment landscape changes (data cutoff: March 20, 2020). During July 2018-February 2020, a total of 185 of 272 patients screened were randomized (niraparib: n = 125 [CR = 1, PR = 124]; placebo: n = 60 [CR = 1, PR = 59]). Median (95% confidence interval [CI]) PFS (blinded independent central review) was 1.54 months (1.41-2.69, niraparib) and 1.36 months (1.31-1.48, placebo); hazard ratio (HR) = 0.66 (95% CI: 0.46-0.95, p = 0.0242). Median overall survival was 9.92 months (9.33-13.54, niraparib) and 11.43 months (9.53-not estimable, placebo); HR = 1.03 (95% CI: 0.62-1.73, p = 0.9052). Median investigator-evaluated PFS was 1.48 months (1.41-2.56, niraparib) and 1.41 months (1.31-2.00, placebo); HR = 0.88 (95% CI: 0.61-1.26; p = 0.4653). Grade greater than or equal to 3 adverse events occurred in 34.4% (niraparib) and 25.0% (placebo) of patients.
ZL-2306-005 did not reach primary end points. Nevertheless, niraparib as maintenance therapy modestly improved PFS in patients with platinum-responsive ES-SCLC, with acceptable tolerability profile and no new safety signal.
ZL-2306-005 是一项随机、双盲、多中心的 3 期研究，旨在评估尼拉帕利（一种聚（二腺苷二磷酸核糖）聚合酶抑制剂）作为中国铂类敏感广泛期小细胞肺癌（ES-SCLC）患者一线维持治疗的疗效和安全性。
完全缓解（CR）或部分缓解（PR）至标准化铂类一线化疗的患者以 2:1 的比例随机接受尼拉帕利或安慰剂（300 mg [基线体重≥77 kg，血小板计数≥150,000/μL]或 200 mg），每日一次，直至疾病进展或不可接受的毒性。主要终点为无进展生存期（PFS）（盲法独立中心评估）和总生存期（计划样本量：591 例）。次要终点包括研究者评估的 PFS 和安全性。
由于 ES-SCLC 治疗格局的变化（数据截止日期：2020 年 3 月 20 日），ZL-2306-005 提前终止。2018 年 7 月至 2020 年 2 月，共有 272 名筛选患者中的 185 名被随机分配（尼拉帕利：n=125 [CR=1，PR=124]；安慰剂：n=60 [CR=1，PR=59]）。盲法独立中心评估的 PFS（中位数[95%置信区间]）为 1.54 个月（1.41-2.69，尼拉帕利）和 1.36 个月（1.31-1.48，安慰剂）；风险比（HR）为 0.66（95%CI：0.46-0.95，p=0.0242）。总生存期的中位数为 9.92 个月（9.33-13.54，尼拉帕利）和 11.43 个月（9.53-不可估计，安慰剂）；HR 为 1.03（95%CI：0.62-1.73，p=0.9052）。研究者评估的 PFS 中位数为 1.48 个月（1.41-2.56，尼拉帕利）和 1.41 个月（1.31-2.00，安慰剂）；HR 为 0.88（95%CI：0.61-1.26；p=0.4653）。≥3 级不良事件发生在 34.4%（尼拉帕利）和 25.0%（安慰剂）的患者中。
ZL-2306-005 未达到主要终点。然而，尼拉帕利作为维持治疗，可适度改善铂类敏感的 ES-SCLC 患者的 PFS，且耐受性良好，无新的安全性信号。
