Osimertinib is largely used as first-line therapy for metastatic epithelial growth factor receptor (EGFR) mutant lung cancers based on the FLAURA clinical trial. Real-world patient outcomes often differ from clinical trial outcomes. This study evaluated the efficacy of first-line osimertinib in patients treated in British Columbia (BC), Canada. Furthermore, we compared the outcomes of patients who would and would not have been eligible for the original FLAURA trial. Consecutive patients receiving first-line osimertinib for metastatic EGFR exon19 or L858R lung cancer were identified using the BC Cancer Pharmacy Database. Patient eligibility for the FLAURA clinical trial were retrospectively reviewed based on the following criteria: ECOG ≥ 2, symptomatic brain metastases or on steroids, hemoglobin < 90 g/L, platelets < 100x10/L, or a creatinine clearance < 50 mL/min. mOS was assessed for the entire population and compared between patients who would have been eligible and ineligible for FLAURA. From January 2020 to October 2021, 311 patients received first-line osimertinib; 44 % (137/311) were deemed FLAURA ineligible, predominantly due to low ECOG (n = 120). After a median follow-up of 26.5 months, the mOS for the entire cohort was 27.4 months (95 %CI 23.8–30.1). The mOS for ineligible patients was 18 months shorter than eligible patients (15.8 vs 34.2, p < 0.001). Ineligible patients had higher rates of de novo stage IV disease, higher rates of stage IVB disease, and more sites of disease than eligible patients. In this real-world population, nearly half of patients would have been ineligible for FLAURA. The mOS was one year shorter than reported in FLAURA. However, patients who would have been eligible for the FLAURA clinical trial had similar OS to patients enrolled in FLAURA. Trial ineligible patients had a higher burden of disease at baseline which may have led to inferior outcomes. Further research is needed to improve outcomes in these patients.

中文翻译：

---

不符合 FLAURA 临床试验资格标准的晚期上皮生长因子受体突变型肺癌患者接受一线奥希替尼治疗的结果

根据 FLAURA 临床试验，奥希替尼主要用作转移性上皮生长因子受体（EGFR）突变型肺癌的一线治疗。现实世界的患者结果通常与临床试验结果不同。本研究评估了一线奥希替尼在加拿大不列颠哥伦比亚省 (BC) 接受治疗的患者中的疗效。此外，我们还比较了符合和不符合最初 FLAURA 试验资格的患者的结果。使用 BC 癌症药房数据库确定了连续接受一线奥希替尼治疗转移性 EGFR 外显子 19 或 L858R 肺癌的患者。根据以下标准对患者参加 FLAURA 临床试验的资格进行回顾性审查：ECOG ≥ 2、有症状的脑转移或使用类固醇、血红蛋白 < 90 g/L、血小板 < 100x10/L 或肌酐清除率 < 50 mL/min。对整个人群的 mOS 进行了评估，并对符合 FLAURA 资格和不符合 FLAURA 资格的患者进行了比较。 2020年1月至2021年10月，311名患者接受一线奥希替尼治疗； 44 % (137/311) 被视为不符合 FLAURA 资格，主要是由于 ECOG 较低 (n = 120)。中位随访 26.5 个月后，整个队列的 mOS 为 27.4 个月 (95% CI 23.8–30.1)。不符合条件的患者的 mOS 比符合条件的患者短 18 个月（15.8 vs 34.2，p < 0.001）。与符合资格的患者相比，不符合资格的患者的 IV 期新发疾病发生率更高，IVB 期疾病发生率更高，并且疾病部位更多。在这个现实世界的人群中，近一半的患者不符合 FLAURA 的资格。 mOS 比 FLAURA 报告的短一年。然而，符合 FLAURA 临床试验资格的患者与参加 FLAURA 的患者具有相似的 OS。不符合试验资格的患者在基线时有较高的疾病负担，这可能导致较差的结果。需要进一步的研究来改善这些患者的治疗结果。