Meng-Xi Zhou, Wen-Jie Fan, Ning Zhang, Li-Yang Zhu, Hong-Yan Wang
Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Front Oncol. 2025 Jan 7;14:1515382. doi: 10.3389/fonc.2024.1515382. eCollection 2024.
Immunotherapy combined with chemoradiotherapy has demonstrated promising efficacy in stage III non-small-cell lung cancer (NSCLC). However, the optimal timing for immunotherapy intervention during radiotherapy remains unclear. This study aimed to compare the efficacy and safety of immune checkpoint inhibitors (ICIs) administered concurrently or sequentially with chemoradiotherapy in unresectable stage III NSCLC.
A retrospective analysis of 98 patients with unresectable stage III NSCLC, treated between January 1, 2019, and June 30, 2023, was conducted. Patients were grouped based on concurrent or sequential administration of ICIs with chemoradiotherapy. Median progression-free survival (mPFS), median overall survival (mOS), 1 and 2-year PFS rates, 2 and 3-year OS rates, objective remission rate (ORR), and disease control rate (DCR) were evaluated. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the log-rank test and Cox proportional hazards model. Treatment-related adverse effects were assessed and graded.
A total of 98 patients with unresectable stage III NSCLC treated with chemoradiotherapy and ICIs were included. The mPFS and mOS were 19.0 (14.2-23.8) months and 31.5 (24.3-38.7) months, 12.8 (9.5-16.1) months and 28.5 (19.3-37.7) months in the concurrent and sequential ICI groups, respectively, and mPFS showed a significant difference (P=0.047). The estimated 1 and 2-year PFS rates were 79.6% (95% confidence interval [CI]: 67.6-91.6) and 40.4% (95% CI: 15.8-49.2) for the concurrent group, compared to 51.0% (95% CI: 35.9-66.1) and 31.6% (95% CI: 14.5-48.7) for the sequential group. The estimated 2 and 3-year OS rates were 65.7% (95% confidence interval [CI]: 48.6-82.8) and 40.0% (95% CI: 16.1-63.9) for the concurrent group, compared to 54.6% (95% CI: 35.8-73.4) and 28.7% (95% CI: 4.8-52.6) for the sequential group. The Eastern Cooperative Oncology Group Performance Status Scale (ECOG) score and tumor differentiation were identified as independent factors associated with PFS and OS. Distant metastasis occurred in 13.8% and 25.5% of patients in the concurrent and sequential ICI groups, respectively (P=0.049). The incidence of any grade of pneumonitis was 43.1% and 38.3% in two groups, with grade 3 or higher in 7.8% and 8.5% of patients, respectively. Hematologic toxicity of any grade was observed in 29.4% and 34.0% of the two groups, with grade 3 or higher toxicity identified in 3.9% and 2.1% of patients, respectively.
Concurrent immunotherapy combined with chemoradiotherapy demonstrated superior efficacy than sequential immunotherapy, with good safety and tolerability in patients with unresectable stage III NSCLC.
免疫疗法联合放化疗已在 III 期非小细胞肺癌（NSCLC）中显示出有前景的疗效。然而，放疗期间免疫疗法干预的最佳时机仍不清楚。本研究旨在比较免疫检查点抑制剂（ICIs）与放化疗同时或序贯给药在不可切除 III 期 NSCLC 中的疗效和安全性。
对 2019 年 1 月 1 日至 2023 年 6 月 30 日期间治疗的 98 例不可切除 III 期 NSCLC 患者进行回顾性分析。根据 ICIs 与放化疗的同时或序贯给药对患者进行分组。评估中位无进展生存期（mPFS）、中位总生存期（mOS）、1 年和 2 年无进展生存率、2 年和 3 年总生存率、客观缓解率（ORR）和疾病控制率（DCR）。使用 Kaplan-Meier 方法进行生存分析。使用对数秩检验和 Cox 比例风险模型进行单因素和多因素分析。评估并分级治疗相关不良反应。
共纳入 98 例接受放化疗和 ICIs 治疗的不可切除 III 期 NSCLC 患者。同时使用 ICI 组和序贯使用 ICI 组的 mPFS 分别为 19.0（14.2 - 23.8）个月和 12.8（9.5 - 16.1）个月，mOS 分别为 31.5（24.3 - 38.7）个月和 28.5（19.3 - 37.7）个月，mPFS 有显著差异（P = 0.047）。同时使用 ICI 组的估计 1 年和 2 年无进展生存率分别为 79.6%（95%置信区间[CI]：67.6 - 91.6）和 40.4%（95%CI：15.8 - 49.2），序贯使用 ICI 组分别为 51.0%（95%CI：35.9 - 66.1）和 31.6%（95%CI：14.5 - 48.7）。同时使用 ICI 组的估计 2 和 3 年总生存率分别为 65.7%（95%置信区间[CI]：48.6 - 82.8）和 40.0%（95%CI：16.1 - 63.9），序贯使用 ICI 组分别为 54.6%（95%CI：35.8 - 73.4）和 28.7%（95%CI：4.8 - 52.6）。东部肿瘤协作组体能状态量表（ECOG）评分和肿瘤分化被确定为与 PFS 和 OS 相关的独立因素。同时使用 ICI 组和序贯使用 ICI 组分别有 13.8%和 25.5%的患者发生远处转移（P = 0.049）。两组任何级别的肺炎发生率分别为 43.1%和 38.3%，3 级或更高级别分别见于 7.8%和 8.5%的患者。两组任何级别的血液学毒性分别见于 29.4%和 34.0%的患者，3 级或更高毒性分别见于 3.9%和 2.1%的患者。
在不可切除 III 期 NSCLC 患者中，免疫疗法与放化疗同时使用显示出比序贯免疫疗法更优的疗效，且安全性和耐受性良好。
