Next-Generation Sequencing Liquid Biopsy-Guided Osimertinib Rechallenge in EGFR-Mutated Advanced Non-Small-Cell Lung Cancer Patients

Vered Fuchs, Waleed Kian, Rachel Lichtenberg, Jonah M. Cooper, Areen A. Remilah, Daniel Levin, Nir Peled, Laila C. Roisman

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background and Objectives: Osimertinib is considered the treatment of choice for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) who progressed on EGFR tyrosine kinase inhibitors (TKIs). It has recently been shown to have superior efficacy over first-/second-generation TKIs as first-line treatment for advanced NSCLC. However, eventual development of resistance to osimertinib is inevitable, amplifying the need for new treatment options in these cases. Rechallenge with early-generation TKIs has been described as an optional treatment method after development of resistance. Nonetheless, osimertinib rechallenge has not yet been widely investigated. Herein, we describe a case series of six patients who, after acquiring resistance to their initial osimertinib treatment, were rechallenged with osimertinib following intervening carboplatin-based chemotherapy. Methods: All patients had advanced NSCLC with a sensitizing EGFR mutation (EGFRm NSCLC). After acquiring resistance to first- or second-line osimertinib treatment, patients were rechallenged with osimertinib 80 mg following a period of carboplatin-based chemotherapy. To track tumor evolution and guide treatment decisions, all patients underwent serial NGS-based liquid biopsy testing throughout their disease course. Results: Six EGFRm NSCLC patients were rechallenged with osimertinib following chemotherapy treatment. Osimertinib was given either as a single agent or as part of combination therapy. Median duration of treatment (DOT) was 5.0 [95% confidence interval (CI) = 2.0–7.0] months and the median OS was 45.0 (95% CI = 34.9–55.1) months. Treatment was generally feasible without serious adverse events. Conclusions: Osimertinib rechallenge as either a single agent or as part of a combination therapy may be an effective and well-tolerated approach with the potential to improve survival by a few months.

Original languageEnglish
Pages (from-to)185-192
Number of pages8
JournalClinical Drug Investigation
Volume42
Issue number2
DOIs
StatePublished - 1 Feb 2022

ASJC Scopus subject areas

  • Pharmacology (medical)

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