Vered Fuchs1, Waleed Kian2, Rachel Lichtenberg3, Jonah M Cooper3, Areen A Remilah2, Daniel Levin4, Nir Peled5, Laila C Roisman2. 1. Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. 2. The Oncology Institute, Shaare Zedek Medical Center, 12, Shmuel Beit St, 9103102, Jerusalem, Israel. 3. Medical School for International Health, Ben-Gurion University of the Negev, Beer Sheva, Israel. 4. The Institute of Nuclear Medicine and Molecular Imaging, Beer-Sheva, Israel. 5. The Oncology Institute, Shaare Zedek Medical Center, 12, Shmuel Beit St, 9103102, Jerusalem, Israel. nirp@szmc.org.il.
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.
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.