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Next-Generation Sequencing Liquid Biopsy-Guided Osimertinib Rechallenge in EGFR-Mutated Advanced Non-Small-Cell Lung
Vered Fuchs1, Waleed Kian2, Rachel Lichtenberg3
1Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
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.
Insights
Osimertinib rechallenge after chemotherapy may extend survival for patients with EGFR-mutated non-small-cell lung cancer (NSCLC) who developed resistance. This approach was feasible and well-tolerated, offering a potential survival benefit.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Osimertinib is a preferred treatment for EGFR-mutated advanced NSCLC after prior TKI failure.
- Resistance to osimertinib inevitably develops, necessitating alternative therapeutic strategies.
- Osimertinib rechallenge is an under-investigated option for managing resistance.
Purpose of the Study:
- To evaluate the efficacy and safety of osimertinib rechallenge in EGFR-mutated NSCLC patients resistant to prior osimertinib treatment.
- To explore the role of intervening carboplatin-based chemotherapy before osimertinib rechallenge.
- To assess survival outcomes and treatment feasibility in this patient population.
Main Methods:
- A case series of six patients with EGFR-mutated advanced NSCLC was analyzed.
- Patients received osimertinib rechallenge (80 mg) after developing resistance to initial osimertinib and undergoing carboplatin-based chemotherapy.
- Serial NGS-based liquid biopsies were performed to monitor tumor evolution.
Main Results:
- Six patients with EGFR-mutated NSCLC were rechallenged with osimertinib post-chemotherapy.
- The median duration of treatment was 5.0 months, and median overall survival was 45.0 months.
- Osimertinib rechallenge was generally feasible and well-tolerated, with no serious adverse events reported.
Conclusions:
- Osimertinib rechallenge, alone or in combination, appears to be an effective and tolerable strategy for patients with EGFR-mutated NSCLC who have developed resistance.
- This approach may offer a survival advantage of several months.
- Further investigation into osimertinib rechallenge is warranted.
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