Phase II Randomized Study of Maintenance Atezolizumab Versus Atezolizumab Plus Talazoparib in Patients With SLFN11 Positive Extensive-Stage SCLC: S1929.

Methods

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.

新诊断的表达SLFN11（H评分≥1，经中心评估）的广泛期小细胞肺癌（ES-SCLC）患者被随机分配到维持atezolizumab（A）与atezolizumab加talazoparib（AT）治疗组，在一线化疗加atezolizumab后。

The primary objective was to compare progression-free survival(PFS) using a one-sided 10% level stratified log-rank test.

主要目标是比较无进展生存期（PFS），使用单侧10%水平的分层对数秩检验。

Secondary endpoints included objective response rate, overall survival, and toxicity.

次要终点包括客观缓解率、总生存期和毒性。

The target sample size was 84 eligible patients.

目标样本量为84名符合条件的患者。

Results

From June 15, 2020, to December 15, 2022, 106 eligible patients were randomized (54 to AT and 52 to A).

从2020年6月15日至2022年12月15日，共有106名符合条件的患者被随机分配（54名至AT组，52名至A组）。

Progression-free survivalwas 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 survivalwas not different between groups (hazard ratio= 0.98, 80% confidence interval: 0.71-1.36, one-sided p = 0.47).

无进展生存期在AT组与A组相比有所改善（风险比=0.66，80%置信区间：0.50-0.86，单侧p=0.019），中位无进展生存期分别为2.9个月和2.4个月；两组之间的总生存期没有差异（风险比=0.98，80%置信区间：0.71-1.36，单侧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.

在AT组和A组中，分别有17%和14%的患者出现了3级及以上的非血液学治疗相关不良事件。

Grade 3 and higher hematological treatment-related adverse events were more common in AT (50%) than in A (4%) (p < 0.001).

在AT治疗组中，3级及以上的血液学治疗相关不良事件的发生率（50%）高于A治疗组（4%）（p < 0.001）。

Conclusions

Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress after initial chemo-immunotherapy.

对于初始化疗免疫治疗后未进展的SLFN11阳性广泛期小细胞肺癌患者，维持AT治疗可改善无进展生存期（PFS）。

Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected.

如预期，与AT治疗相关的血液毒性增加，主要是3级贫血。

Prospective biomarker selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.

展示了前瞻性生物标志物选择，为未来在分子定义的小细胞肺癌人群中评估新疗法铺平了道路。