Protocol for a systematic review with prospective individual patient data meta-analysis in EGFR-mutant NSCLC with brain metastases to assess the effect of SRS+osimertinib compared to osimertinib alone: the STARLET Collaboration

• Published in: BMJ open Vol. 14; no. 7; p. e078335
• Main Authors: Robledo, Kristy P, Lefresne, Shilo, Soon, Yu Yang, Sahgal, Arjun, Pinkham, Mark B, Nichol, Alan, Soo, Ross Andrew, Parmar, Ambika, Hegi-Johnson, Fiona, Doherty, Mark, Solomon, Benjamin J, Shultz, David B, Tham, Ivan WK, Sacher, Adrian G, Tey, Jeremy, Leong, Cheng Nang, Koh, Wee Yao, Huang, Yiqing, Ang, Yvonne Li En, Low, Jiali, Yong, Clement, Lim, Mei Chin, Tan, Ai Peng, Lee, Chee Khoon, Ho, Cheryl
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 05.07.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Protocol
• Subjects: Acrylamides - therapeutic use; Aniline Compounds - therapeutic use; Antineoplastic Agents - therapeutic use; Asymptomatic; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - secondary; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - secondary; Clinical trials; Collaboration; Combined Modality Therapy; ErbB Receptors - genetics; Humans; Indoles; Kinases; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Meta-Analysis; Meta-Analysis as Topic; Metastasis; Mutation; Oncology; Patients; Prospective Studies; Pyrimidines; Radiation oncology; Radiation therapy; Radiosurgery; Radiosurgery - methods; Randomized Controlled Trials as Topic; Research Design; Respiratory tract tumours; Response rates; Statistical power; Systematic review; Systematic Reviews as Topic; Targeted cancer therapy; Web portals; Clinical trials; Respiratory tract tumours; Meta-Analysis; ONCOLOGY; Radiation oncology; Patients
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2023-078335

BackgroundPatients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice.MethodsRandomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform’s Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups.Ethics and disseminationApproved by each trial’s ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases.Prospero registrationCRD42022330532.