Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany.
Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.
Invest New Drugs. 2021 Aug;39(4):1189-1196. doi: 10.1007/s10637-021-01091-9. Epub 2021 Mar 11.
The aim of this prospective study is to evaluate the clinical use and real-world efficacy of durvalumab maintenance treatment after chemoradiotherapy (CRT) in unresectable stage, locally advanced non-small cell lung cancer (NSCLC). All consecutive patients with unresectable, locally advanced NSCLC and PD-L1 expression (≥1%) treated after October 2018 were included. Regular follow up, including physical examination, PET/CT and/or contrast-enhanced CT-Thorax/Abdomen were performed every three months after CRT. Descriptive treatment pattern analyses, including reasons of discontinuation and salvage treatment, were undertaken. Statistics were calculated from the last day of thoracic irradiation (TRT). Twenty-six patients were included. Median follow up achieved 20.6 months (range: 1.9-30.6). Durvalumab was initiated after a median of 25 (range: 13-103) days after completion of CRT. In median 14 (range: 2-24) cycles of durvalumab were applied within 6.4 (range 1-12.7) months. Six patients (23%) are still in treatment and seven (27%) have completed treatment with 24 cycles. Maintenance treatment was discontinued in 13 (50%) patients: 4 (15%) patients developed grade 3 pneumonitis according to CTCAE v5 after a median of 3.9 (range: 0.5-11.6) months and 7 (range: 2-17) cycles of durvalumab. Four (15%) patients developed grade 2 skin toxicity. One (4%) patient has discontinued treatment due to incompliance. Six and 12- month progression-free survival (PFS) rates were 82% and 62%, median PFS was not reached. No case of hyperprogression was documented. Eight (31%) patients have relapsed during maintenance treatment after a median of 4.8 (range: 2.2-11.3) months and 11 (range: 6-17) durvalumab cycles. Two patients (9%) developed a local-regional recurrence after 14 and 17 cycles of durvalumab. Extracranial distant metastases and brain metastases as first site of failure were detected in 4 (15%) and 2 (8%) patients, respectively. Three (13%) patients presented with symptomatic relapse. Our prospective study confirmed a favourable safety profile of durvalumab maintenance treatment after completion of CRT in unresectable stage, locally advanced NSCLC in a real-world setting. In a median follow-up time of 20.6 months, durvalumab was discontinued in 27% of all patients due to progressive disease. All patients with progressive disease were eligible for second-line treatment.
本前瞻性研究旨在评估 durvalumab 维持治疗在不可切除的局部晚期非小细胞肺癌（NSCLC）患者接受放化疗（CRT）后的临床应用和真实世界疗效。所有接受 2018 年 10 月后治疗的不可切除、局部晚期 NSCLC 且 PD-L1 表达（≥1%）的连续患者均被纳入。在 CRT 后每三个月进行一次常规随访，包括体检、PET/CT 和/或对比增强 CT-胸部/腹部。进行了描述性的治疗模式分析，包括停药和挽救治疗的原因。统计数据从胸部放疗（TRT）的最后一天开始计算。共纳入 26 例患者。中位随访时间达到 20.6 个月（范围：1.9-30.6）。在 CRT 完成后中位数 25 天（范围：13-103 天）开始使用 durvalumab。在中位数 14 天（范围：2-24 天）内应用了中位数 14 个（范围：2-12.7）个周期的 durvalumab。6 例（23%）患者仍在治疗中，7 例（27%）患者完成了 24 个周期的治疗。13 例（50%）患者停止了维持治疗：4 例（15%）患者在中位数 3.9 个月（范围：0.5-11.6）和中位数 7 个（范围：2-17 个）周期 durvalumab 后根据 CTCAE v5 出现 3 级肺炎。4 例（15%）患者出现 2 级皮肤毒性。1 例（4%）患者因不遵医嘱而停止治疗。6 个月和 12 个月无进展生存率（PFS）分别为 82%和 62%，中位 PFS 未达到。未发现超进展病例。8 例（31%）患者在维持治疗期间发生复发，中位数时间为 4.8 个月（范围：2.2-11.3）和中位数 11 个周期（范围：6-17 个）durvalumab。2 例（9%）患者在接受 14 和 17 个 durvalumab 周期后出现局部区域复发。4 例（15%）和 2 例（8%）患者分别出现颅外远处转移和脑转移作为首次失败部位。3 例（13%）患者出现症状性复发。我们的前瞻性研究在真实世界环境中证实了 durvalumab 在不可切除的局部晚期 NSCLC 患者 CRT 后的维持治疗具有良好的安全性。在中位随访时间为 20.6 个月时，由于疾病进展，所有患者中有 27%的患者停止了 durvalumab 治疗。所有疾病进展的患者均有资格接受二线治疗。
