HALT: targeted therapy with or without dose-intensified radiotherapy in oligo-progressive disease in oncogene addicted lung tumours

Abstract

Introduction: Following initial response to TKI, advanced NSCLC patients with actionable mutations will ultimately develop treatment resistance. In a proportion of patients (15–40%), limited progression (≤3 lesions) is initially observed, termed oligoprogressive disease (OPD). Optimal management of these patients is uncertain, with subsequent systemic therapy options limited in the UK. The potential benefit offered by SBRT to ablate OPD sites prior to change in systemic therapy is an important question to address. HALT is designed to assess whether SBRT treatment to OPD sites can increase the time patients derive clinical benefit from TKI therapy until further disease progression Methods: HALT is a randomised, multi-centre, phase II/III trial with seamless transition to phase III incorporated. International participation is established via a UK-led (ICR, NCRI Lung CSG, RTTQA) intergroup collaboration with European coordinating groups (EORTC and SAKK). Eligible patients (Stage IV NSCLC, actionable mutation, initial TKI response prior to OPD) are randomised 2:1 to SBRT and continued TKI or continued TKI alone. Follow-up aligned with routine care at 3 monthly intervals until change in systemic therapy is clinically indicated, with imaging and toxicity assessment at each visit. Results: HALT opened for recruitment November 2017; 19 centres (14 UK; 5 non-UK) are open to date (30/09/2019) with 43 patients registered and 26 randomised. A virtual MDT comprising trial clinicians and radiologists convenes remotely to confirm eligibility (OPD; SBRT suitability). Of 43 patients registered vMDT review has been performed for 37 (6 screen fails prior to vMDT review); 26 patients randomised and 11 confirmed ineligible via vMDT. Conclusion: The vMDT remains an important novel aspect of the trial, ensuring robust patient selection ahead of randomisation. As the first randomised trial assessing the benefit of SBRT in this patient population, HALT will provide valuable treatment efficacy and safety information, informing the design of an international phase III trial.