Osimertinib and Etoposide as First-Line Treatment in Osimertinib-Resistant Advanced EGFR-Mutant NSCLC

Osimertinib, though a standard first-line treatment for EGFR-mutant advanced NSCLC, shows primary resistance in 10-30% of patients, leading to disease progression within 3-4 months. This resistance is linked to co-mutations in genes like TP53, RB1, and PIK3CA, among others. Studies indicate that Topo II inhibitor Etoposide (VP-16) can reduce cell survival, enhance DNA damage, and delay resistance in Osimertinib-resistant cells, suggesting a potential combination therapy to manage resistance.This study is a single-center, prospective, single-arm study evaluating the efficacy and safety of osimertinib combined with etoposide as a first-line treatment in patients with osimertinib-resistant or -insensitive advanced non-small cell lung cancer (NSCLC). The study focuses on patients with advanced NSCLC (stage IIIB or IV) with EGFR-sensitive mutations who developed slow resistance to osimertinib and for whom secondary biopsy after resistance did not identify any therapeutic targets.

NCT Number	NCT06436144
Lead Sponsor	Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Conditions	Non Small Cell Lung Cancer, EGFR Gene Mutation, Non Small Cell Lung Cancer Stage IIIB, Non-small Cell Lung Cancer Stage IV
Enrollment	93 participants
Start Date	2024-06
Primary Completion	2029-06 (estimated)
Study Completion	2029-12 (estimated)
Updated on ClinicalTrials.gov	2024-05-30