JTO Clinical and Research Reports (Jun 2022)

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

  • A.J. Piper-Vallillo, MD,
  • Julia K. Rotow, MD,
  • Jacqueline V. Aredo, MD,
  • Khvaramze Shaverdashvili, MD, PhD,
  • Jia Luo, MD,
  • Jennifer W. Carlisle, MD,
  • Hatim Husain, MD,
  • Alona Muzikansky, MA,
  • Rebecca S. Heist, MD,
  • Deepa Rangachari, MD,
  • Suresh S. Ramalingam, MD,
  • Heather A. Wakelee, MD,
  • Helena A. Yu, MD,
  • Lecia V. Sequist, MD,
  • Joshua M. Bauml, MD,
  • Joel W. Neal, MD, PhD,
  • Zofia Piotrowska, MD, MHS

Journal volume & issue
Vol. 3, no. 6
p. 100328

Abstract

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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.

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