EORTC-1537-COBRA phase II: Very early PET-guided therapy in advanced-stage cHL

Primary results from the single-arm, multicenter, phase II EORTC-1537-COBRA trial (NCT03517137) evaluating very early [¹⁸F]fluorodeoxyglucose positron emission tomography–computed tomography ([¹⁸F]FDG-PET–CT)-guided treatment adaptation in adults with previously untreated, advanced-stage classical Hodgkin lymphoma (cHL), were published in The Lancet Haematology by Hutchings et al. Following one cycle of brentuximab vedotin + doxorubicin + vinblastine + dacarbazine (A-AVD), PET1-negative patients (n = 90; 60%) continued A-AVD, while PET1-positive patients (n = 60; 40%) switched to brentuximab vedotin + etoposide + cyclophosphamide + doxorubicin + dacarbazine + dexamethasone (BrECADD). The primary endpoint was 2-year modified progression-free survival (mPFS) in evaluable patients (n = 145).

Key data: At a median follow-up of 30.1 months, the 2-year mPFS was 89.5% (80% confidence interval [CI], 85.7–92.4), meeting the predefined success criterion; 2-year overall survival (OS) was 100%. By PET1 status, 2-year mPFS was 88.3% (95% CI, 79.4–93.5) with continued A-AVD and 91.3% (95% CI, 80.3–96.3) following switch to BrECADD. Positive serum thymus and activation-regulated chemokine (sTARC) after one cycle was associated with PET1 positivity (odds ratio [OR], 2.3; 95% CI, 1.0–5.2; p = 0.048). Grade 3–4 adverse events (AEs) occurred in 63%, most commonly neutropenia (35%) and anemia (12%); serious AEs occurred in 30%, with no treatment-related deaths.

Key learning: Very early PET-guided intensification to BrECADD achieved high clinical activity in advanced-stage cHL while sparing most patients intensive chemotherapy.