Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy.
Division of Medical Oncology 2, Veneto Institute of Oncology - IRCCS, Padova, Italy.
Oncologist. 2022 Mar 4;27(2):87-e115. doi: 10.1002/onco.13951.
Osimertinib became the standard treatment for patients with untreated EGFR-mutant advanced non-small cell lung cancer (aNSCLC) following results reported in the phase III randomized FLAURA trial. Because of strict exclusion criteria, patient populations included in pivotal trials are only partially representative of real-world patients.
We designed an observational, prospective, multicenter study enrolling patients with EGFR-mutant aNSCLC receiving first-line osimertinib to evaluate effectiveness, safety, and progression patterns in the real-world.
At data cutoff, 126 White patients from nine oncology centers were included. At diagnosis, 16 patients (12.7%) had a performance status (PS) ≥2 and 38 (30.2%) had brain metastases. Overall response rate (ORR) was 73%, disease control rate (DCR) 96.0%. After a median follow-up of 12.3 months, median time to treatment discontinuation (mTTD) was 25.3 months, median progression-free-survival (mPFS) was 18.9 months and median overall survival (mOS) was not reached (NR). One hundred and ten patients (87%) experienced adverse events (AEs), 42 (33%) of grade 3-4, with venous thromboembolism (VTE) as the most common (n = 10, 7.9%). No difference in rates of VTE was reported according to age, PS, comorbidity, and tumor load. We observed longer mTTD in patients without symptoms (NR vs. 18.8 months) and with fewer than three metastatic sites at diagnosis (NR vs. 21.4 months). Patients without brain metastases experienced longer mPFS (NR vs. 13.3 months). No difference in survival outcome was observed according to age, comorbidity, and type of EGFR mutation. Isolated progression and progression in fewer than three sites were associated with longer time to treatment discontinuation (TTD).
Osimertinib confirmed effectiveness and safety in the real world, although thromboembolism was more frequent than previously reported.
在 III 期随机 FLAURA 试验报告结果后，奥希替尼成为未经治疗的 EGFR 突变型晚期非小细胞肺癌（aNSCLC）患者的标准治疗方法。由于严格的排除标准，关键性试验中纳入的患者人群仅部分代表真实世界的患者。
我们设计了一项观察性、前瞻性、多中心研究，招募接受一线奥希替尼治疗的 EGFR 突变型 aNSCLC 患者，以评估真实世界中的疗效、安全性和进展模式。
截至数据截止日期，来自 9 个肿瘤中心的 126 名白人患者被纳入研究。在诊断时，16 名患者（12.7%）的体能状态（PS）≥2，38 名患者（30.2%）有脑转移。总缓解率（ORR）为 73%，疾病控制率（DCR）为 96.0%。中位随访 12.3 个月后，中位治疗停药时间（mTTD）为 25.3 个月，中位无进展生存期（mPFS）为 18.9 个月，中位总生存期（mOS）未达到（NR）。110 名患者（87%）发生不良事件（AE），42 名（33%）为 3-4 级，其中静脉血栓栓塞（VTE）最为常见（n=10，7.9%）。根据年龄、PS、合并症和肿瘤负荷，VTE 发生率无差异。我们观察到无症状患者的 mTTD 更长（NR 与 18.8 个月），诊断时转移部位少于 3 个的患者 mTTD 更长（NR 与 21.4 个月）。无脑转移的患者 mPFS 更长（NR 与 13.3 个月）。年龄、合并症和 EGFR 突变类型对生存结果无影响。孤立性进展和少于 3 个部位的进展与更长的 TTD 相关。
奥希替尼在真实世界中证实了疗效和安全性，尽管血栓栓塞的发生率高于先前报告。
