Piper-Vallillo A J, Rotow Julia K, Aredo Jacqueline V, Shaverdashvili Khvaramze, Luo Jia, Carlisle Jennifer W, Husain Hatim, Muzikansky Alona, Heist Rebecca S, Rangachari Deepa, Ramalingam Suresh S, Wakelee Heather A, Yu Helena A, Sequist Lecia V, Bauml Joshua M, Neal Joel W, Piotrowska Zofia
Massachusetts General Hospital, Boston, Massachusetts.
Beth Israel Deaconess Medical Center, Boston, Massachusetts.
JTO Clin Res Rep. 2022 Apr 21;3(6):100328. doi: 10.1016/j.jtocrr.2022.100328. eCollection 2022 Jun.
This multicenter review evaluated the efficacy and safety of osimertinib dose escalation for central nervous system (CNS) progression developing on osimertinib 80 mg in -mutant NSCLC.
Retrospective review identified 105 patients from eight institutions with advanced -mutant NSCLC treated with osimertinib 160 mg daily between October 2013 and January 2020. Radiographic responses were clinically assessed, and Kaplan-Meier analyses were used. We defined CNS disease control as the interval from osimertinib 160 mg initiation to CNS progression or discontinuation of osimertinib 160 mg.
Among 105 patients treated with osimertinib 160 mg, 69 were escalated for CNS progression, including 24 treated with dose escalation alone (cohort A), 34 who received dose-escalated osimertinib plus concurrent chemotherapy and/or radiation (cohort B), and 11 who received osimertinib 160 mg without any prior 80 mg exposure. The median duration of CNS control was 3.8 months (95% confidence interval [CI], 1.7-5.8) in cohort A, 5.1 months (95% CI, 3.1-6.5) in cohort B, and 4.2 months (95% CI 1.6-not reached) in cohort C. Across all cohorts, the median duration of CNS control was 6.0 months (95% CI, 5.1-9.0) in isolated leptomeningeal progression (n = 27) and 3.3 months (95% CI, 1.0-3.1) among those with parenchymal-only metastases (n = 23). Patients on osimertinib 160 mg experienced no severe or unexpected side effects.
Among patients with -mutant NSCLC experiencing CNS progression on osimertinib 80 mg daily, dose escalation to 160 mg provided modest benefit with CNS control lasting approximately 3 to 6 months and seemed more effective in patients with isolated leptomeningeal CNS progression.
本多中心回顾性研究评估了奥希替尼剂量递增对在接受80毫克奥希替尼治疗时出现中枢神经系统（CNS）进展的EGFR突变型非小细胞肺癌（NSCLC）患者的疗效和安全性。
回顾性研究纳入了2013年10月至2020年1月期间在8家机构接受每日160毫克奥希替尼治疗的105例晚期EGFR突变型NSCLC患者。通过临床评估影像学反应，并采用Kaplan-Meier分析方法。我们将CNS疾病控制定义为从开始使用160毫克奥希替尼至CNS进展或停用160毫克奥希替尼的时间间隔。
在105例接受160毫克奥希替尼治疗的患者中，69例因CNS进展而进行了剂量递增，其中24例仅接受剂量递增治疗（A组），34例接受了剂量递增的奥希替尼联合同步化疗和/或放疗（B组），11例在未接受过任何80毫克奥希替尼治疗的情况下直接接受160毫克奥希替尼治疗（C组）。A组CNS控制的中位持续时间为3.8个月（95%置信区间[CI]，1.7 - 5.8），B组为5.1个月（95% CI，3.1 - 6.5），C组为4.2个月（95% CI 1.6 - 未达到）。在所有队列中，孤立性软脑膜转移患者（n = 27）的CNS控制中位持续时间为6.0个月（95% CI，5.1 - 9.0），仅实质性转移患者（n = 23）为3.3个月（95% CI，1.0 - 3.1）。接受160毫克奥希替尼治疗的患者未出现严重或意外的副作用。
在每日接受80毫克奥希替尼治疗时出现CNS进展的EGFR突变型NSCLC患者中，将剂量递增至160毫克可带来适度益处，CNS控制持续约3至6个月，且对孤立性软脑膜CNS进展患者似乎更有效。
