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. 2022 Apr 21;3(6):100328.
doi: 10.1016/j.jtocrr.2022.100328. eCollection 2022 Jun.

High-Dose Osimertinib for CNS Progression in EGFR+ NSCLC: A Multi-Institutional Experience

A J Piper-Vallillo  1   2 , Julia K Rotow  3   4 , Jacqueline V Aredo  5 , Khvaramze Shaverdashvili  6 , Jia Luo  3   4   7 , Jennifer W Carlisle  8 , Hatim Husain  9 , Alona Muzikansky  1 , Rebecca S Heist  1   3 , Deepa Rangachari  2   3 , Suresh S Ramalingam  8 , Heather A Wakelee  5 , Helena A Yu  7 , Lecia V Sequist  1   3 , Joshua M Bauml  6 , Joel W Neal  5 , Zofia Piotrowska  1   3
Affiliations

High-Dose Osimertinib for CNS Progression in EGFR+ NSCLC: A Multi-Institutional Experience

A J Piper-Vallillo et al. JTO Clin Res Rep. .

Abstract

Introduction: This multicenter review evaluated the efficacy and safety of osimertinib dose escalation for central nervous system (CNS) progression developing on osimertinib 80 mg in EGFR-mutant NSCLC.

Methods: Retrospective review identified 105 patients from eight institutions with advanced EGFR-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.

Results: 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.

Conclusion: Among patients with EGFR-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.

Keywords: 160 mg; CNS progression; EGFR; Leptomeningeal progression; Osimertinib.

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Figures

Figure 1
Figure 1
Treatment-based cohort assignments. Patients were assigned to cohorts A, B, or C according to treatment with osimertinib 80 mg before CNS PD and concurrent chemotherapy or RT at the time of CNS PD. Chemo, chemotherapy; CNS, central nervous system; Osi, osimertinib; PD, disease progression; RT, radiation therapy.
See this image and copyright information in PMC

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