About this trial
This study involves patients with EGFR-mutated NSCLC and asymptomatic brain metastases. This is an open-label, randomized study, comparing the continuation of Osimertinib treatment alone to Osimertinib treatment combined with early intervention stereotactic radiosurgery (SRS). The current first line of care for EGFR-mutated NSCLC is administration of Osimertinib, a small molecule that penetrates the blood brain barrier (BBB) well and controls majority, but not all, of the brain metastases. We hypothesize that relatively early intervention with SRS to brain metastases that are still visualized by MRI 2 months-post initiation of Osimertinib treatment, LUNG- will improve long term brain control, cognitive abilities and potentially overall survival. Patients with EGFR-mutated NSCLC and asymptomatic brain metastases will be treated with Osimertinib for 2 months. Brain MRI scans will be collected pre-Osimertinib and 2 months after treatment start. Patients with asymptomatic brain metastases present after 2 months of Osimertinib will be randomized into one of two study arms. Arm A patients will be treated with SRS while continuing Osimertinib, while arm B patients will continue with Osimertinib alone. Patients will be assessed based on brain and whole body progression by RECIST. Patients will also be assessed for CNS-PFS and body-PFS, cognitive function, Quality of life and overall survival status via routine follow-up tests.
Eligibility criteria
Qualifiers
Newly diagnosed metastatic NSCLC, not amenable to curative surgery or curative radiotherapy.
Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be sensitive to Osimertinib - These include exon 19 del; L858R (exon 21); G719X (exon 18); L861G (exon 21); S768I (exon 20) and T790M (exon 20) NOTE: Mutation analysis is to be done as per local practice.
An MRI showing brain metastases. At randomization, number of brain lesions is under 20. Patients with over 20 brain lesions at randomization MRI will be suitable for whole brain radiation, and will not be randomized.
Brain metastases are asymptomatic or with minor symptoms (ECOG≤2) at study randomization.
Disqualifiers
Anti EGFR TKI treatment.
Checkpoint inhibitors immunotherapy for metastatic NSCLC.
Whole brain radiation (WBRT) and/or Stereotactic Radiosurgery (SRS).
Medications or herbal supplements known to be potent inducers of CYP3A4 and are unable to stop use within the recommended wash out period prior to receiving the first dose of Osimertinib.
Trial design
Treatments tested in this trial
- Stereotactic surgery