Background: Platinum-based chemotherapy is the current standard treatment option in patients withEGFR-mutant non-small-cell lung cancer (NSCLC) who progress on osimertinib. However, outcomes with chemotherapy are dismal, and the treatment of central nervous system (CNS) disease is an unmet need in this setting. Methods: Patients withEGFR-mutant NSCLC who were candidates to receive osimertinib in the metastatic setting at our Center from 2015 to 2022 were retrospectively evaluated to identify patients who received standard platinum-based chemotherapy post-osimertinib. Data were collected on treatment outcomes, with a focus on brain metastases and progression patterns. Results: A total of 220 patients received indication for osimertinib in the study period;n= 176 had adequate follow-up data. Overall,n= 117 patients experienced disease progression on osimertinib. The median time to osimertinib progressive disease (PD) was 15 months (95% confidence interval CI 13–18). Of them, 51 patients (45%) had no access to further treatments. Of the remaining patients,n= 8 received experimental treatments, andn= 55 received standard platinum-based chemotherapy and were considered for this study. Median duration of chemotherapy was 3 months (95% CI 2–5); the best responses among 53 evaluable patients were observed as follows: 15% partial response/complete response (PR/CR), 40% stable disease (SD), 45% PD. Median progression-free survival (PFS) and overall survival (OS) were 3 (95% CI 2–5) and 10 (95% CI 6–15) months, respectively. All patients had baseline and follow-up brain radiologic assessments, and n = 23 had brain metastases at the start of chemotherapy. With a median follow-up of 13 months, intracranial PD occurred in 47% patients, being the first site of PD in 59% of cases. The median time for intracranial (IC) PD was 2 months (95% CI 2–7). IC PD occurred as oligometastatic in 29%, whereas in 71% of cases, it was associated with systemic PD. Conclusions: Access to subsequent treatments and CNS progression are confirmed unmet needs inEGFR-mutant NSCLC patients. Clinical and CNS-specific outcomes in patients receiving standard chemotherapy after the failure of osimertinib are dismal. Novel upfront treatment options with demonstrated prolonged PFS and better CNS outcomes may help address this important issue.
背景：对于奥希替尼治疗后进展的EGFR突变非小细胞肺癌（NSCLC）患者，铂类化疗是目前的标准治疗方案。然而，化疗疗效欠佳，且中枢神经系统（CNS）疾病治疗仍是该领域未被满足的临床需求。方法：本研究回顾性分析2015年至2022年期间在本中心接受奥希替尼治疗的转移性EGFR突变NSCLC患者，筛选出奥希替尼治疗后接受标准铂类化疗的病例。收集治疗结果数据，重点关注脑转移及疾病进展模式。结果：研究期间共220例患者符合奥希替尼治疗指征，其中176例具有完整随访数据。总体而言，117例患者在奥希替尼治疗期间出现疾病进展，中位进展时间为15个月（95%置信区间13-18）。其中51例（45%）患者未接受后续治疗。其余患者中，8例接受实验性治疗，55例接受标准铂类化疗并纳入本研究分析。化疗中位持续时间为3个月（95%置信区间2-5）；53例可评估患者的最佳疗效为：部分缓解/完全缓解（PR/CR）15%，疾病稳定（SD）40%，疾病进展（PD）45%。中位无进展生存期（PFS）和总生存期（OS）分别为3个月（95%置信区间2-5）和10个月（95%置信区间6-15）。所有患者均接受基线及随访脑部影像学评估，其中23例在化疗开始时存在脑转移。中位随访13个月期间，47%患者出现颅内进展，其中59%以颅内进展为首发进展部位。颅内进展中位时间为2个月（95%置信区间2-7）。29%的颅内进展表现为寡转移，而71%伴随全身性进展。结论：后续治疗的可及性与CNS进展确认为EGFR突变NSCLC患者未被满足的临床需求。奥希替尼治疗失败后接受标准化疗患者的临床结局及CNS特异性疗效均不理想。具有延长PFS和改善CNS疗效的新型一线治疗方案可能有助于解决这一重要临床问题。
Post-Progression Analysis ofEGFR-Mutant NSCLC Following Osimertinib Therapy in Real-World Settings
肿瘤(癌症)患者之家