Acker Fabian, Reck Martin, Martin Daniel, Rieken Stefan, Heinzen Sophie, Rost Maximilian, Aguinarte Lukas, Schulte Hanna, Serve Hubert, Oellerich Thomas, Sebastian Martin, Althoff Friederike C
Goethe University Frankfurt, University Hospital, Department of Medicine II, Hematology and Oncology, Frankfurt, Germany.
LungenClinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
Eur J Cancer. 2025 Mar 11;218:115266. doi: 10.1016/j.ejca.2025.115266. Epub 2025 Jan 30.
In patients with unresectable, stage III non-small cell lung cancer (NSCLC), durvalumab maintenance after concurrent chemoradiotherapy (cCRT) was shown to improve survival over placebo. As subgroup analyses indicated better outcomes with earlier start of durvalumab, several trials evaluated concomitant checkpoint inhibition (CPI) with cCRT. However, this may introduce an increased risk of treatment-related pulmonary toxicity.
We conducted a systematic review and meta-analysis of clinical trials of combined cCRT plus CPI followed by CPI maintenance in patients with stage III NSCLC. Endpoints included incidence of pneumonitis by any cause, objective response rate (ORR), progression-free (PFS), and overall survival (OS).
A total of 7 trials comprising 653 patients were included. In trials of single-agent CPI with cCRT, pneumonitis occurred in 33 % of patients (95 % confidence interval [CI], 28-39) with 7 % (5-9) having CTCAE grade 3-5. In one trial, double CPI (PD-1 and CTLA4) plus cCRT was associated with excessive pneumonitis-related mortality of 16 % (4-40). Across all trials, ORR was 69 % (63-76). Median PFS and OS were 16.3 (95 % CI, 14.0-20.5) and 39.5 months (35.3-45.9), respectively. Three-year PFS and OS were 36.8 % (95 % CI, 32.7-41.4) and 53.1 % (49.1-57.4). Sensitivity analysis showed that induction chemoimmunotherapy prior cCRT plus CPI was associated with improved PFS of 48.0 % at 3 years (95 % CI, 40.7-56.7) in one trial.
Addition of single-agent CPI to cCRT is manageable in selected patients with stage III NSCLC. Efficacy outcomes appear to be in line with previous data of cCRT followed by CPI maintenance.
在不可切除的 III 期非小细胞肺癌（NSCLC）患者中，同步放化疗（cCRT）后使用度伐利尤单抗维持治疗相较于安慰剂可改善生存期。亚组分析表明，更早开始使用度伐利尤单抗预后更佳，因此多项试验评估了 cCRT 联合检查点抑制剂（CPI）的疗效。然而，这可能会增加治疗相关肺部毒性的风险。
我们对 III 期 NSCLC 患者接受 cCRT 联合 CPI 治疗后再进行 CPI 维持治疗的临床试验进行了系统评价和荟萃分析。研究终点包括任何原因引起的肺炎发生率、客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。
共纳入 7 项试验，涉及 653 例患者。在 cCRT 联合单药 CPI 的试验中，33%的患者发生肺炎（95%置信区间[CI]，28 - 39），其中 7%（5 - 9）的患者 CTCAE 分级为 3 - 5 级。在一项试验中，双 CPI（PD - 1 和 CTLA4）联合 cCRT 导致与肺炎相关的死亡率过高，达 16%（4 - 40）。在所有试验中，ORR 为 69%（63 - 76）。PFS 中位数和 OS 分别为 16.3 个月（95%CI，14.0 - 20.5）和 39.5 个月（35.3 - 45.9）。3 年 PFS 和 OS 分别为 36.8%（95%CI，32.7 - 41.4）和 53.1%（49.1 - 57.4）。敏感性分析显示，在一项试验中，cCRT 联合 CPI 之前进行诱导化疗免疫治疗与 3 年 PFS 改善 48.0%（95%CI，40.7 - 56.7）相关。
在部分 III 期 NSCLC 患者中，cCRT 联合单药 CPI 治疗是可行的。疗效结果似乎与先前 cCRT 后进行 CPI 维持治疗的数据一致。
