Purpose: Targeted therapies (TT) and immune checkpoint blockers (ICB) have revolutionized the approach to non–small cell lung cancer (NSCLC) treatment in the era of precision medicine. Their impact as switch maintenance therapy based on molecular characterization is unknown. Patients and Methods: SAFIR02-Lung/IFCT 1301 was an open-label, randomized, phase II trial, involving 33 centers in France. We investigated eight TT (substudy-1) and one ICB (substudy-2), compared with standard-of-care as a maintenance strategy in patients with advanced EGFR, ALK wild-type (wt) NSCLC without progression after first-line chemotherapy, based on high-throughput genome analysis. The primary outcome was progression-free survival (PFS). Results: Among the 175 patients randomized in substudy-1, 116 received TT (selumetinib, vistusertib, capivasertib, AZD4547, AZD8931, vandetanib, olaparib, savolitinib) and 59 standard-of-care. Median PFS was 2.7 months [95% confidence interval (CI), 1.6–2.9] with TT versus 2.7 months (1.6–4.1) with standard-of-care (HR, 0.97; 95% CI, 0.7–1.36; P = 0.87). There were no significant differences in PFS within any molecular subgroup. In substudy-2, 183 patients were randomized, 121 received durvalumab and 62 standard-of-care. Median PFS was 3.0 months (2.3–4.4) with durvalumab versus 3.0 months (2.0–5.1) with standard-of-care (HR, 0.86; 95% CI, 0.62–1.20; P = 0.38). Preplanned subgroup analysis showed an enhanced benefit with durvalumab in patients with PD-L1 tumor proportion score (TPS) ≥1%, (n = 29; HR, 0.29; 95% CI, 0.11–0.75) as compared with PD-L1 <1% (n = 31; HR, 0.71; 95% CI, 0.31–1.60; Pinteraction = 0.036). Conclusions: Molecular profiling can feasibly be implemented to guide treatment choice for the maintenance strategy in EGFR/ALK wt NSCLC; in this study it did not lead to substantial treatment benefits beyond durvalumab for PD-L1 ≥ 1 patients.

中文翻译：

---

转移性非小细胞肺癌患者的全面基因组分析：精准医学 II 期随机 SAFIR02-Lung/IFCT 1301 试验

目的：靶向治疗（TT）和免疫检查点阻断剂（ICB）彻底改变了精准医疗时代非小细胞肺癌（NSCLC）的治疗方法。它们作为基于分子特征的转换维持疗法的影响尚不清楚。患者和方法：SAFIR02-Lung/IFCT 1301 是一项开放标签、随机、II 期试验，涉及法国 33 个中心。我们研究了 8 项 TT（子研究 1）和 1 项 ICB（子研究 2），与标准护理作为一线化疗后无进展的晚期 EGFR、ALK 野生型 (wt) NSCLC 患者的维持策略进行比较，基于高通量基因组分析。主要结局是无进展生存期（PFS）。结果：在子研究 1 中随机分配的 175 名患者中，116 名患者接受了 TT（selumetinib、vistusertib、capivasertib、AZD4547、AZD8931、vandetanib、olaparib、savolitinib）和 59 标准护理。TT 组的中位 PFS 为 2.7 个月 [95% 置信区间 (CI)，1.6–2.9]，而标准护理组的中位 PFS 为 2.7 个月 (1.6–4.1)（HR，0.97；95% CI，0.7–1.36；P = 0.87 ）。任何分子亚组内的 PFS 均无显着差异。在子研究 2 中，183 名患者被随机分组​​，其中 121 名患者接受 durvalumab，62 名患者接受标准治疗。durvalumab 组的中位 PFS 为 3.0 个月 (2.3–4.4)，而标准护理组的中位 PFS 为 3.0 个月 (2.0–5.1)（HR，0.86；95% CI，0.62–1.20；P = 0.38）。预先计划的亚组分析显示，与 PD-L1 肿瘤比例评分 (TPS) ≥1%（n = 29；HR，0.29；95% CI，0.11-0.75）的患者相比，durvalumab 的获益增强。 1%（n = 31；HR，0.71；95% CI，0.31–1.60；Pinteraction = 0.036）。结论：分子谱分析可以切实可行地指导 EGFR/ALK wt NSCLC 维持策略的治疗选择；在这项研究中，对于 PD-L1 ≥ 1 的患者，除了 durvalumab 之外，它没有带来实质性的治疗益处。