Stanford University School of Medicine, Stanford, California.
Department of Medical Oncology & Therapeutics Research, City of Hope Medical Center, Duarte, California.
J Thorac Oncol. 2021 Jun;16(6):1030-1041. doi: 10.1016/j.jtho.2021.01.1628. Epub 2021 Feb 12.
In 2018, durvalumab was approved by the U.S. Food and Drug Administration as consolidation immunotherapy for patients with stage III NSCLC after definitive chemoradiotherapy (CRT). However, whether durvalumab benefits patients with EGFR-mutated NSCLC remains unknown.
We conducted a multi-institutional retrospective analysis of patients with unresectable stage III EGFR-mutated NSCLC who completed concurrent CRT. Kaplan-Meier analyses evaluated progression-free survival (PFS) between patients who completed CRT with or without durvalumab.
Among 37 patients, 13 initiated durvalumab a median of 20 days after CRT completion. Two patients completed 12 months of treatment, with five patients discontinuing durvalumab owing to progression and five owing to immune-related adverse events (irAEs). Of 24 patients who completed CRT without durvalumab, 16 completed CRT alone and eight completed CRT with induction or consolidation EGFR tyrosine kinase inhibitors (TKIs). Median PFS was 10.3 months in patients who received CRT and durvalumab versus 6.9 months with CRT alone (log-rank p = 0.993). CRT and EGFR TKI was associated with a significantly longer median PFS (26.1 mo) compared with CRT and durvalumab or CRT alone (log-rank p = 0.023). Six patients treated with durvalumab initiated EGFR TKIs after recurrence, with one developing grade 4 pneumonitis on osimertinib.
In this study, patients with EGFR-mutated NSCLC did not benefit with consolidation durvalumab and experienced a high frequency of irAEs. Patients who initiate osimertinib after durvalumab may be susceptible to incident irAEs. Consolidation durvalumab should be approached with caution in this setting and concurrent CRT with induction or consolidation EGFR TKIs further investigated as definitive treatment.
2018 年，美国食品和药物管理局批准 durvalumab 用于接受根治性放化疗（CRT）后的 III 期非小细胞肺癌（NSCLC）患者的巩固免疫治疗。然而，durvalumab 是否对 EGFR 突变型 NSCLC 患者有益尚不清楚。
我们对完成同步 CRT 的不可切除 III 期 EGFR 突变型 NSCLC 患者进行了多机构回顾性分析。Kaplan-Meier 分析评估了完成 CRT 并接受或未接受 durvalumab 治疗的患者之间的无进展生存期（PFS）。
在 37 例患者中，有 13 例患者在 CRT 完成后中位数 20 天开始接受 durvalumab 治疗。2 例患者完成了 12 个月的治疗，5 例患者因疾病进展和 5 例因免疫相关不良反应（irAEs）停止 durvalumab 治疗。在未接受 durvalumab 治疗的 24 例患者中，16 例单独接受 CRT，8 例接受 CRT 联合诱导或巩固 EGFR 酪氨酸激酶抑制剂（TKI）治疗。接受 CRT 和 durvalumab 治疗的患者中位 PFS 为 10.3 个月，而单独接受 CRT 的患者中位 PFS 为 6.9 个月（对数秩检验 p=0.993）。与 CRT 和 durvalumab 或 CRT 单药治疗相比，CRT 和 EGFR TKI 治疗与显著更长的中位 PFS（26.1 个月）相关（对数秩检验 p=0.023）。6 例接受 durvalumab 治疗的患者在复发后开始使用 EGFR TKI，其中 1 例在使用奥希替尼时发生 4 级肺炎。
在这项研究中，EGFR 突变型 NSCLC 患者并未从巩固性 durvalumab 治疗中获益，并且发生 irAEs 的频率较高。在 durvalumab 后开始使用 osimertinib 的患者可能易发生新的 irAEs。在这种情况下，应谨慎使用 durvalumab 巩固治疗，并进一步研究同步 CRT 联合诱导或巩固 EGFR TKI 作为确定性治疗。
