Combinatie van zes geneesmiddelen (BrECADD) resulteert in betere overleving met minder bijwerkingen bij patiënten met gevorderde lymfklierkanker van het type Hodgkinlymfoom in vergelijking met BEACOPP regiem

12 juni 2024: Bron: ASCO 2024

Het BrECADD-regiem, een combinatie van zes geneesmiddelen, te weten brentuximab, vedotin, etoposide, cyclofosfamide, doxorubicine, dacarbazine en dexamethason, verbetert overall overleving en vermindert het risico op ziekteprogressie met minder bijwerkingen in vergelijking met het BEACOPP-regiem (bleomycine, etoposide, doxorubicine, cyclofosfamide, vincristine, procarbazine, prednison) voor de meeste patiënten met gevorderde lymfklierkanker van het type klassieke Hodgkinlymfoom.

Peter Borchmann, M.D., van het Universitair Ziekenhuis van Keulen in Duitsland, en collega's beoordeelden in hun studie of het nieuwe BrECADD-regiem, geleid door positronemissietomografie (PET) na twee cycli, de behandeling van patiënten met gevorderde lymfklierkanker van het type klassieke Hodgkinlymfoom zou kunnen verbeteren. De analyse omvatte 1.482 patiënten met gevorderde Hodgkinlymfoom (AS-cHL) (in de leeftijd van 18 tot 60 jaar) die willekeurig werden toegewezen aan vier of zes cycli van het BrECADD-regiem of BEACOPP-regiem.

De onderzoekers ontdekten dat tijdens een mediane studie follow-up van 48 maanden de vierjaars progressievrije overleving (PFS) 94,3 procent bedroeg voor patiënten die het BrECADD-regiem kregen en 90,9 procent voor degenen die het BEACOPP-regiem kregen (hazard ratio, 0,66; P = 0,035).

Het voordeel van BrECADD werd veroorzaakt door een consistente vermindering van het falen van de vroege behandeling, inclusief primaire progressie binnen drie maanden (vijf versus 15 maanden) of een vroege terugval tussen maand 3 en 12 (11 versus 23 maanden) in alle subgroepen.
Patiënten in de BrECADD-groep die na twee cycli negatief waren op de PET-scan, hadden een vierjaars ziekteprogressievrije tijd (PFS) van 96,5 procent. Voor degenen die het BrECADD-regiem kregen, was de totale vierjaarsoverleving 98,5 procent versus 98,2 procent voor patiënten die het BEACOPP-regiem kregen.

De onderzoekers ontdekten ook dat ernstige bloedgerelateerde bijwerkingen minder optraden bij patiënten van de BrECADD-groep (31 procent) versus 52 procent in de BEACOPP-groep, wat zich vertaalde in minder transfusies van rode bloedcellen en bloedplaatjes in de BrECADD-groep.
Hogere herstelpercentages van het follikelstimulerende hormoon werden na één jaar gezien bij zowel mannen (67 versus 24 procent) als vrouwen (89 versus 68 procent). Hogere geboortecijfers werden ook gezien in de BrECADD-groep (60 versus 43 geboorten).

Het abstract van de studie werd gepresenteeerd op ASCO 2024.

Tolerability and efficacy of BrECADD versus BEACOPP in advanced stage classical Hodgkin lymphoma: GHSG HD21, a randomized study.

Authors

Peter Borchmann, Alden A Moccia, Richard Greil, Gundolf Schneider, Mark Hertzberg, Valdete Schaub, Andreas Huettmann, Felix Keil, Judith Dierlamm, Mathias Haenel, Julia Meissner, Stephan Mathas, Josee M Zijlstra, Alexander Fosså, Justin Ferdinandus, Michael Fuchs, Wolfram Klapper, Hans-Theodor Eich, Carsten Kobe, Volker Diehl

Organizations

University Hospital of Cologne, and Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), and German Hodgkin Study Group (GHSG), Cologne, Germany, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland, Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectious Disease, Rheumatology, Oncologic Center, Laboratory for Immunological and Molecular Cancer Research, Paracelsus Medical University, Salzburg Cancer Research, Salzburg, Austria, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Department I of Internal Medicine, and Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), and German Hodgkin Study Group (GHSG), Cologne, Germany, Prince of Wales Hospital, Department of Haematology, and Australasian Leukaemia & Lymphoma Group, Sidney, Australia, University of Tuebingen, Tuebingen, Germany, Department of Haematology, University Hospital, University Duisburg-Essen, Essen, Germany, Department of Haematology, Hanusch Krankenhaus, Vienna, Austria, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department III of Internal Medicine, University Hospital Chemnitz, Chemnitz, Germany, Department of Hematology and Oncology, University of Heidelberg, Heidelberg, Germany, Charité - Universitätsmedizin Berlin, Hematology, Oncology and Tumor Immunology, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany, VU University Medical Center, Amsterdam, Netherlands, Department of Oncology, Oslo University Hospital, Oslo, Norway and Nordic Lymphoma Group, Oslo, Norway, Department of Pathology, Division of Hematopathology and Lymph Node Registry, Schleswig-Holstein Medical Center, Campus Kiel, Kiel, Germany, Department of Radiotherapy, University Hospital of Muenster, Münster, Germany, Department of Nuclear Medicine, University Hospital of Cologne, Cologne, and Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), and German Hodgkin Study Group (GHSG), Cologne, Germany

Abstract Disclosures

Research Funding

Takeda Oncology

Background:We hypothesized that therapy with the novel BrECADD regimen (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) guided by positron emission tomography after two cycles (PET2) could improve the treatment of advanced-stage classical Hodgkin lymphoma (AS-cHL). The HD21 trial aimed at demonstrating superiority over the intensified BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) in terms of treatment-related morbidity (TRMB) and non-inferiority (NI) in terms of progression-free survival (PFS). This is the first report of the final confirmative analysis of the HD21 trial.Methods:HD21 is an international, open-label, randomized phase III trial including AS-cHL patients 18-60 years at diagnosis. Patients were randomized to receive individualized 4 or 6 cycles of either BEACOPP or BrECADD guided by PET2 results. The co-primary endpoints included TRMB and PFS, which had been successfully established recently. Testing for superiority was planned with mature follow-up of four years. An adjusted alpha level of 0.047 was required to cross the efficacy boundary for superiority. The trial was conducted in accordance with ICH-GCP (NCT02661503) and supported by a research grant from Takeda Oncology.Results:The ITT (intention-to-treat) cohort for the efficacy analysis consisted of 1482 patients, of which 742 were randomized to receive BrECADD and 740 to BEACOPP. Median age was 31.1 years (range 18 to 60), 44% were female. PET2 was negative in 424 (57.5%) and 426 (58.2%) patients for BrECADD or eBEACOPP, respectively, and these were scheduled for 4 treatment cycles. With median follow-up of 48 months, 4y-PFS was 94.3% for BrECADD (95%-CI 92.6-96.1), and 90.9% for BEACOPP (95%-CI 88.7-93.1). The hazard ratio was 0.66 [95% CI 0.45-0.97], p=0.035). PFS benefit of BrECADD was driven by a reduction in early treatment failures, i.e., primary progression within 3 months (5 vs. 15) or early relapse between months 3 and 12 (11 vs. 23) and observed across all investigated subgroups. PET2-negative patients in the BrECADD group showed a 4-year PFS of 96.5%. 4-year OS was 98.5% for BrECADD and 98.2% for BEACOPP. Analyses of gonadal function demonstrated significantly higher follicle stimulating hormone recovery rates after one year in both men (67% vs. 24%) and women (89% vs. 68%) with higher birth-rates in the BrECADD group (n=60 vs. n=43).Conclusions:BrECADD is significantly more effective than BEACOPP and is associated with an unprecedentedly high 4-year PFS, reducing the risk of progression, relapse or death by a third. Together with an abbreviated treatment duration of only 3 months for the majority of patients and a favorable tolerability, treatment with PET2-individualized BrECADD sets a new benchmark for the treatment of adult patients with AS-cHL. Clinical trial information: NCT02661503.