P025: RADAR: An international phase III, PET response-adapted, randomised trial in progress, comparing ABVD±ISRT with brentuximab vedotin+AVD±ISRT in patients with previously untreated limited-stage classical Hodgkin lymphoma

Abstract

Figure 1: RADAR trial schema Background: Limited-stage classical Hodgkin lymphoma (lsHL), stages I or II without B-symptoms or mediastinal bulk disease, has excellent long-term survival (≥90%) with modern treatment. Commonly used approaches, based on GSHG and EORTC trials, include 2–4 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) plus 20 or 30 Gy radiotherapy (RT), but there are concerns about the impact of using RT in all patients (pts) on the incidence of 2nd cancers and cardiovascular disease. In the UK NCRI RAPID trial, pts who had a -ve PET scan after 3 cycles of ABVD were randomised between RT and no RT; outcomes in the no RT arm were very good but the non-inferiority margin of -7% was not achieved. The RADAR trial is building on the PET-adapted approach of RAPID but intending to make the chemotherapy more effective by replacing bleomycin with the CD30 targeted antibody drug conjugate, brentuximab vedotin (BV), in the BV+AVD regimen. Early phase trials of BV+AVD in lsHL and the phase III ECHELON-1 trial in advanced HL have demonstrated its efficacy and safety. In addition, RT will be integrated on an individualised basis to pts in RADAR who are PET -ve after initial chemotherapy but with larger nodal masses at baseline. Methods: RADAR comprises 2 parallel identical phase III randomised multicentre trials in the UK, Europe, Australia, New Zealand (trial 1; 642 pts), Canada and the USA (trial 2; 400 pts). Eligibility: age 16–69 years, previously untreated stage IA/IIA HL above the diaphragm, any mediastinal mass ≤0.33 of internal thoracic diameter, informed consent. Pts will be randomised to receive either ABVD or BV+AVD. A centrally-reviewed PET-CT scan after cycle 2 (PET2) will determine further treatment (Deauville score (DS) 1–3: total 3 cycles +/- individualised RT; DS 4: total 4 cycles + 30 Gy ISRT; DS 5: treatment failure, subsequent treatment of clinician’s choice). 1y endpoint is progression free survival (PFS) and the trial will have 85% power to show an improvement from 90 to 95% PFS at 3 years (HR of 0.49) with 2-sided 5% alpha. 2y endpoints are CMR rate at PET2, event-free survival (progression, death, PET2 DS 4–5), OS, safety and toxicity including cardiovascular disease and second cancers. Exploratory endpoints: predictive value of PET after 1 cycle, prognostic value of baseline metabolic tumour volume. Embedded translational research aims to identify biomarkers predictive of treatment failure. RADAR opened to recruitment in April 2022.