在不可切除的III期ALK阳性NSCLC化疗后，联合ALK酪氨酸激酶抑制剂对比Durvalumab或观察

晚期ALK阳性非小细胞肺癌（NSCLC）患者通常对免疫治疗的反应较差；对于不可切除的III期ALK阳性NSCLC患者，联合治疗使用Durvalumab的益处尚不明确。在此，我们比较了化放疗后使用ALK酪氨酸激酶抑制剂（TKI）、Durvalumab或观察的疗效和安全性。

We conducted a retrospective study using a multicenter study of 17 institutions globally. Patients with unresectable stage III ALK-positive NSCLC treated between 2015 and 2022 were included. Patients received ALK TKI, durvalumab, or observation after concurrent chemoradiation. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related adverse events (trAEs) were classified by Common Terminology Criteria for Adverse Events version 5.0. Outcomes were assessed by multivariable Cox regression analysis.

我们进行了一项回顾性研究，数据来源于全球17家机构的多中心研究。纳入了2015年至2022年间接受治疗的不可切除III期ALK阳性非小细胞肺癌（NSCLC）患者。患者在同步放化疗后接受了ALK酪氨酸激酶抑制剂（TKI）、Durvalumab或观察。使用Kaplan-Meier方法估计真实世界中的无进展生存期（rwPFS）和总生存期（OS）。治疗相关的不良事件（trAEs）按照不良事件通用术语标准（CTCAE）第5.0版进行分类。通过多变量Cox回归分析评估研究结果。

A total of 67 patients were included, of whom 39 (58%) were female. Median age was 57 (interquartile range: 49–67) years. Furthermore, 15 received consolidation ALK TKI, 30 received durvalumab, and 22 underwent observation. Baseline characteristics were similar across the three groups other than differences in race. After adjusting for stage, age, and nodal status, median rwPFS was significantly longer for ALK TKI (rwPFS not reached, 95% confidence interval [CI]: 22.7– not reached) versus durvalumab (11.3 mo, 95% CI: 8.9–18.5, hazard ratio [HR] = 0.12, 95% CI: 0.026–0.5, p-adjusted [p-adj] = 0.006) or observation (7.2 mo, 95% CI: 3.4–10.6, HR = 0.04, 95% CI: 0.009–0.2, p-adj < 0.0001). Durvalumab significantly improved median rwPFS compared with observation (HR = 0.37, 95% CI: 0.19–0.71, p-adj = 0.002). Median OS in the ALK TKI and durvalumab cohorts was significantly improved compared with patients on observation (ALK TKI-observation: p = 0.04; durvalumab-observation: p = 0.03). TrAE of any grade occurred in eight (53%) and 11 (37%) patients treated with ALK TKI and durvalumab, respectively. Grade greater than or equal to three trAEs occurred in 27% (n = 4) of patients treated with ALK TKI and 6.7% of patients treated with durvalumab.

研究共纳入67名患者，其中39名（58%）为女性。中位年龄为57岁（四分位距：49–67岁）。此外，15名患者接受了ALK TKI巩固治疗，30名患者接受了Durvalumab治疗，22名患者进行了观察。三组患者的基线特征相似，除了种族的差异。经过对分期、年龄和淋巴结状态的调整后，ALK TKI组的中位真实世界无进展生存期（rwPFS）显著延长（rwPFS尚未达到，95%置信区间 [CI]：22.7–尚未达到），与Durvalumab组（11.3个月，95% CI：8.9–18.5，风险比 [HR] = 0.12，95% CI：0.026–0.5，p调整值 [p-adj] = 0.006）或观察组（7.2个月，95% CI：3.4–10.6，HR = 0.04，95% CI：0.009–0.2，p-adj < 0.0001）相比有显著差异。与观察组相比，Durvalumab显著改善了中位rwPFS（HR = 0.37，95% CI：0.19–0.71，p-adj = 0.002）。ALK TKI组和Durvalumab组的中位总生存期（OS）与观察组相比显著改善（ALK TKI-观察组：p = 0.04；Durvalumab-观察组：p = 0.03）。在接受ALK TKI治疗的患者中，有8名（53%）出现了任何级别的治疗相关不良事件（trAE），而接受Durvalumab治疗的患者中有11名（37%）出现了trAE。接受ALK TKI治疗的患者中，有27%（n = 4）出现了3级或以上的trAE，而接受Durvalumab治疗的患者中有6.7%出现了同样级别的不良事件。

Patients with ALK-positive NSCLC experience significantly improved rwPFS when treated with consolidation ALK TKI therapy, surpassing outcomes found with either durvalumab or observation. Although both ALK TKI therapy and durvalumab offer an extension in OS compared with observation alone, it seems that ALK TKI therapy is the superior choice, underscoring its pivotal role in enhancing patient survival.

ALK阳性NSCLC患者在接受ALK TKI巩固治疗时，真实世界无进展生存期（rwPFS）显著改善，优于Durvalumab或观察组的结果。尽管与单纯观察相比，ALK TKI治疗和Durvalumab都延长了总生存期（OS），但ALK TKI治疗似乎是更优的选择，突显了其在提高患者生存率方面的重要作用。