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ABVD (8 cycles) versus BEACOPP (4 escalated cycles => 4 baseline) in stage III-IV high-risk Hodgkin lymphoma (HL): First results of EORTC 20012 Intergroup randomized phase III clinical trial.
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2012
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Beacopp PtsPrimary EndpointCancer ManagementClinical EndpointPathologyTreatment VerificationHematological MalignancyRadiation MedicineOncologyHematologyClinical TrialsOs SuperiorityRadiation OncologyEortc 20012Cancer ResearchHealth SciencesLymphoid NeoplasiaOutcomes ResearchCancer TreatmentLung CancerFirst ResultsPrognostic EvaluationVersus BeacoppMedicine
8002 Background: Escalated BEACOPP and derivatives achieved superior time to treatment failure (FFTF) over COPP/ABVD, resulting in higher overall survival (OS) for advanced HL. However, later clinical trials have failed to confirm OS superiority over ABVD. Methods: Eligibility criteria: clinical stage III/IV HL, International prognostic score (IPS) ≥ 3, age<60. We compared ABVD (8 cycles) vs. BEACOPP (escalated 4 cycles ≥ baseline 4), without irradiation. Randomization was stratified for institution and IPS. Primary endpoint was EFS, defined as treatment discontinuation, no complete response (CR) after 8 cycles, progression, relapse or death. Additional endpoints were CR, progression free survival (PFS), OS, quality of life and secondary malignancies. Outcomes were reviewed by study coordinators to ensure consistency across pts. Results: From 2002-2010, 549 pts were randomized (ABVD 275, BEACOPP 274): stage IV 74%, PS 0, 1, 2: 34, 48 and 17%, B-symptoms 81%, median age 35.2y, males 75%. IPS was 4 or higher for 59% of pts. Histology reviewed no HL in 4 cases. CR was 83% in both arms. With a median follow-up of 3.8 yrs, EFS at 4 yrs was 63.7% vs. 69.3% (HR = 0.86, 95%CI=0.64 to 1.15, p=0.312). PFS at 4 yrs was 72.8% vs. 83.4% (HR = 0.58, 95%CI=0.39 to 0.85, p=0.005). OS at 4 yrs was 86.7 vs. 90.3 (HR = 0.71, 95%CI=0.42 to 1.21, p=0.208). Toxic deaths occurred in 6 and 5 pts, with early discontinuation (prior to cycle 5) in 12 & 26 pts, respectively. There were 5 crossovers to BEACOPP and 10 to ABVD. Second malignancies occurred in 8 ABVD and 10 BEACOPP pts (myelodysplasia/leukemia 2 and 4, lung 2 and 1, NHL 3 and 2, other 1 and 3); cumulative incidence curves did not differ significantly. Conclusions: The primary endpoint (EFS) was similar between treatment arms. However, more progressions/relapses were observed with ABVD, while early discontinuations were more frequent with BEACOPP. Nevertheless, even in this high-risk group, OS was not improved with BEACOPP. Additional considerations (treatment burden and cost, fertility issues, long term relapses and immediate and late morbidity) may guide physician/patient decisions toward ABVD or BEACOPP.