Karim Nagla Abdel, Miao Jieling, Reckamp Karen L, Gay Carl M, Byers Lauren A, Zhao Ying-Qi, Redman Mary W, Carrizosa Daniel R, Wang Wei-Lien, Petty William J, Mehta Kathan, Faller Bryan A, Agamah Edem S, Kasbari Samer S, Malisetti Rajini K, Kumar Atul, Schallenkamp John, Alluri Krishna C, Gray Jhanelle E, Kelly Karen
Inova Schar Cancer Institute, Fairfax, Virginia; University of Virginia, Fairfax, Virginia.
SWOG Statistical Center and Data Management Center, Seattle, Washington; Fred Hutchinson Cancer Center, Seattle, Washington.
J Thorac Oncol. 2025 Mar;20(3):383-394. doi: 10.1016/j.jtho.2024.10.021. Epub 2024 Nov 4.
To evaluate whether the addition of a poly (adenosine diphosphate-ribose) polymerase inhibitor talazoparib to maintenance immune checkpoint inhibitor atezolizumab after frontline chemoimmunotherapy improved outcomes in patients with Schlafen 11 (SLFN11)-positive extensive-stage SCLC (ES-SCLC).
Patients with newly diagnosed SLFN11 expressing (H-score ≥ 1, evaluated centrally) ES-SCLC were randomized to maintenance atezolizumab (A) versus atezolizumab plus talazoparib (AT) after frontline chemotherapy plus atezolizumab. The primary objective was to compare progression-free survival (PFS) using a one-sided 10% level stratified log-rank test. Secondary endpoints included objective response rate, overall survival, and toxicity. The target sample size was 84 eligible patients.
From June 15, 2020, to December 15, 2022, 106 eligible patients were randomized (54 to AT and 52 to A). Progression-free survival was improved with AT versus A (hazard ratio = 0.66, 80% confidence interval: 0.50-0.86, one-sided p = 0.019) with a median PFS of 2.9 and 2.4 months; overall survival was not different between groups (hazard ratio = 0.98, 80% confidence interval: 0.71-1.36, one-sided p = 0.47). Grade 3 and higher non-hematologic treatment-related adverse events occurred in 17% of patients with AT and 14% of patients with A. Grade 3 and higher hematological treatment-related adverse events were more common in AT (50%) than in A (4%) (p < 0.001).
Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress after initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.
评估在一线化疗免疫治疗后，将聚（二磷酸腺苷 - 核糖）聚合酶抑制剂他拉唑帕利添加到维持免疫检查点抑制剂阿替利珠单抗中，是否能改善含 Schlafen 11（SLFN11）的广泛期小细胞肺癌（ES - SCLC）患者的预后。
将新诊断为表达 SLFN11（中心评估H评分≥1）的ES - SCLC患者在一线化疗加阿替利珠单抗后随机分为阿替利珠单抗维持治疗组（A组）和阿替利珠单抗联合他拉唑帕利维持治疗组（AT组）。主要目标是使用单侧10%水平分层对数秩检验比较无进展生存期（PFS）。次要终点包括客观缓解率、总生存期和毒性。目标样本量为84例符合条件的患者。
从2020年6月15日至2022年12月15日，106例符合条件的患者被随机分组（54例分到AT组，52例分到A组）。与A组相比，AT组的无进展生存期得到改善（风险比 = 0.66，80%置信区间：0.50 - 0.86，单侧p = 0.019），中位PFS分别为2.9个月和2.4个月；两组总生存期无差异（风险比 = 0.98，80%置信区间：0.71 - 1.36，单侧p = 0.47）。AT组17%的患者和A组14%的患者发生3级及以上非血液学治疗相关不良事件。3级及以上血液学治疗相关不良事件在AT组（50%）比A组（4%）更常见（p < 0.001）。
维持治疗AT可改善初始化疗免疫治疗后未进展的SLFN11阳性ES - SCLC患者的PFS。正如预期的那样，AT组血液学毒性增加，主要是3级贫血。研究展示了前瞻性生物标志物选择，为未来在分子定义的SCLC人群中评估新疗法铺平了道路。
