TARGET: A Phase II, Open-Label, Single-Arm Study of 5-Year Adjuvant Osimertinib in Completely Resected EGFR-Mutated Stage II to IIIB NSCLC Post Complete Surgical Resection.

INTRODUCTION: Osimertinib is a central nervous system (CNS)-active, third generation, irreversible, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR-TKI sensitizing and EGFR T790M resistance mutations, with demonstrated efficacy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). We present the rationale and design for TARGET (NCT05526755), which will evaluate the efficacy and safety of 5 years of adjuvant osimertinib in patients with completely resected EGFRm stage II to IIIB NSCLC. MATERIALS AND METHODS: TARGET is a phase II, multinational, open-label, single-arm study. Adults aged ≥18 years (Taiwan ≥20 years), with resected stage II to IIIB NSCLC are eligible; prior adjuvant chemotherapy is allowed. Eligible patients must have locally confirmed common (exon 19 deletion or L858R) or uncommon (G719X, L861Q, and/or S768I) EGFR-TKI sensitizing mutations, alone or in combination. Patients will receive osimertinib 80 mg once daily for 5 years or until disease recurrence, discontinuation or death. The primary endpoint is investigator-assessed disease-free survival (DFS) at 5 years (common EGFR mutations cohort). Secondary endpoints include: investigator-assessed DFS at 3 and 4 years; overall survival at 3, 4, and 5 years (common EGFR mutations cohort); DFS at 3, 4, and 5 years (uncommon EGFR mutations cohort); safety and tolerability, type of recurrence and CNS metastases (both cohorts). Exploratory endpoints include: tissue/plasma concordance; analysis of circulating molecules in plasma samples using different profiling approaches to detect minimal residual disease; incidence and change over time of incidental pulmonary nodules. RESULTS: TARGET is currently recruiting, and completion is expected in 2029.

A real-world study of second or later-line osimertinib in patients with EGFR T790M-positive NSCLC: the final ASTRIS data.

Aim: Report the final analysis from ASTRIS, the largest real-world study of second-/later-line osimertinib in advanced/metastatic EGFR T790M non-small-cell lung cancer (NSCLC). Methods: Patients with advanced/metastatic EGFR T790M NSCLC and prior EGFR-TKI treatment, received once-daily osimertinib 80 mg. Primary end point: overall survival (OS); secondary end points: progression-free survival (PFS), time-to-treatment discontinuation (TTD) and response rate. Safety was also recorded. Results: In 3014 patients, median OS: 22.8 months (21.6-23.8), median PFS: 11.1 months (11.0-12.0), median TTD: 13.5 months (12.6-13.9), and response rate: 57.3% (55.5-59.2). All end points reported with 95% CIs. Numerically longer median OS was observed in patients with baseline WHO performance status <2 versus 2 (24.0 vs 11.1 months) and those without versus with brain/leptomeningeal metastases (25.4 vs 18.0 months). No new safety signals were identified. Conclusion: Second-/later-line osimertinib demonstrated real-world clinical benefit and safety in advanced/metastatic EGFR T790M NSCLC. Clinical Trial Registration: NCT02474355 (ClinicalTrials.gov).

Osimertinib is a drug that blocks the activity of a protein called EGFR on cancer cells, reducing their growth and spread. ASTRIS is the largest real-world study that evaluated the outcomes with osimertinib treatment for patients with advanced non-small-cell lung cancer (NSCLC), and the EGFR T790M mutation, who had received previous treatment for their cancer. There were 3014 patients included in this study. The main aim of this study was to measure the time at which half of the patients were still alive after starting osimertinib treatment, this was 22.8 months. The study also measured the time at which half of the patients had experienced worsening (progression) of their cancer (11.1 months) and the time when half of the patients had stopped receiving osimertinib treatment (13.5 months). None of the patients experienced any unexpected side effects of the treatment. These data are consistent with those observed in comparable clinical trials with osimertinib, supporting the use of osimertinib treatment for patients with advanced NSCLC and the EGFR T790M mutation after their initial cancer treatment has stopped working.

Characteristics and overall survival of patients with early-stage non-small cell lung cancer: A cohort study in Denmark.

Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer diagnoses, and approximately 35% of patients with NSCLC are diagnosed at an early stage (I-IIIA). This study aimed to describe epidermal growth factor receptor (EGFR) testing, patient characteristics, and overall survival (OS) among patients with early-stage NSCLC in Denmark. Patients with early-stage NSCLC registered in the Danish Lung Cancer Registry in 2013-2018 were followed through 2019. We described EGFR testing, descriptively summarised patient characteristics, and calculated OS by EGFR testing and mutation status. The association between EGFR mutation (EGFRm) and all-cause mortality was estimated using Cox proportional-hazards regression, in subgroups defined by stage at diagnosis, age at diagnosis, comorbidity, and receipt of surgery. In 2013-2018, 21,282 patients with NSCLC were registered in the Danish Lung Cancer Registry, of whom 8758 were diagnosed at an early stage. Of those, 4071 (46%) were tested for EGFRm at diagnosis. Median OS was 5.7 years among patients with EGFRm-positive status (n = 361) and 4.4 years among patients with EGFRm-negative status (n = 3710). EGFRm-positive status was associated with lower all-cause mortality in all subgroups. This study contributes to population-based evidence on the epidemiology of early-stage NSCLC treated in routine clinical practice.