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

Abstract

Background: Following initial response to TKI, advanced NSCLC patients with actionable mutations ultimately develop treatment resistance. In a proportion of patients (15-40%), initial, limited pro gression (≤3 lesions) is observed, termed oligoprogressive disease (OPD). SBRT offers hypofractionated, targeted radiotherapy treatment hypothesised to prolong clinical benefit from TKI prior to widespread disease development. The potential benefit offered by SBRT to ablate OPD sites prior to change in systemic therapy is an important question to address, particularly during the current pandemic, where reducing clinic visits is particularly advantageous. Method: HALT is a randomised, multi-centre, phase II/III international trial with seamless transition to phase III incorporated. Eligible patients (stage IV NSCLC, actionable mutation, TKI response prior to OPD) are randomised 2:1 to SBRT/continued TKI or continued TKI alone. Eligibility is confirmed by a virtual MDT comprising trial clinicians and radiologists (OPD, SBRT suitability). Follow-up assessments aligned with routine care at 3-monthly intervals until change in systemic therapy is clinically indicated, imaging and toxicity assessment at each visit. Current status: Recruitment commenced November 2017; 27 centres (16 UK; 11 non-UK) open to date (09/03/2021), 94 patients registered and 50 randomised. Because of the COVID-19 pandemic, recruitment was temporarily paused on 20/03/2020 and restarted in accordance with national guidelines on 16/06/2020. Of 94 patients registered, vMDT review performed for 74 patients (18 screen fails prior to vMDT); 50 randomised, 22 confirmed ineligible via vMDT (inc. >3 lesions, lesion >5cm, intracranial disease identified). Conclusion: The vMDT remains an important, novel aspect of the trial, ensuring robust patient selection ahead of randomisation. As the first randomised trial assessing SBRT benefit in this patient population, HALT will provide valuable treatment efficacy and safety information, informing subsequent trial design and contribute to the development of international guidelines for the identification and clinical management of oligoprogression in mutation positive lung cancer.