TY - JOUR
T1 - Next-Generation Sequencing Liquid Biopsy-Guided Osimertinib Rechallenge in EGFR-Mutated Advanced Non-Small-Cell Lung Cancer Patients
AU - Fuchs, Vered
AU - Kian, Waleed
AU - Lichtenberg, Rachel
AU - Cooper, Jonah M.
AU - Remilah, Areen A.
AU - Levin, Daniel
AU - Peled, Nir
AU - Roisman, Laila C.
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85123219810&partnerID=8YFLogxK
U2 - 10.1007/s40261-021-01116-4
DO - 10.1007/s40261-021-01116-4
M3 - Article
C2 - 35044639
AN - SCOPUS:85123219810
SN - 1173-2563
VL - 42
SP - 185
EP - 192
JO - Clinical Drug Investigation
JF - Clinical Drug Investigation
IS - 2
ER -
