In this parallel group, open-label, multicentre, non-inferiority trial (HD15), 2182 patients with newly diagnosed advanced stage Hodgkin's lymphoma aged 18-60 years were randomly assigned to receive either eight cycles of BEACOPPescalated (8脳Besc group), six cycles of BEACOPPescalated (6脳Besc group), or eight cycles of BEACOPP14 (8脳B14 group). Randomisation (1:1:1) was done centrally by stratified minimisation. Non-inferiority of the primary endpoint, freedom from treatment failure, was assessed using repeated CIs for the hazard ratio (HR) according to the intention-to-treat principle. Patients with a persistent mass after chemotherapy measuring 2路5 cm or larger and positive on PET scan received additional radiotherapy with 30 Gy; the negative predictive value for tumour recurrence of PET at 12 months was an independent endpoint. This trial is registered with Current Controlled Trials, number ISRCTN32443041.
Of the 2182 patients enrolled in the study, 2126 patients were included in the intention-to-treat analysis set, 705 in the 8脳Besc group, 711 in the 6脳Besc group, and 710 in the 8脳B14 group. Freedom from treatment failure was sequentially non-inferior for the 6脳Besc and 8脳B14 groups as compared with 8脳Besc. 5-year freedom from treatment failure rates were 84路4%(97路5%CI 81路0-87路7) for the 8脳Besc group, 89路3%(86路5-92路1) for 6脳Besc group, and 85路4%(82路1-88路7) for the 8脳B14 group (97路5%CI for difference between 6脳Besc and 8脳Besc was 0路5-9路3). Overall survival in the three groups was 91路9%, 95路3%, and 94路5%respectively, and was significantly better with 6脳Besc than with 8脳Besc (97路5%CI 0路2-6路5). The 8脳Besc group showed a higher mortality (7路5%) than the 6脳Besc (4路6%) and 8脳B14 (5路2%) groups, mainly due to differences in treatment-related events (2路1%, 0路8%, and 0路8%, respectively) and secondary malignancies (1路8%, 0路7%, and 1路1%, respectively). The negative predictive value for PET at 12 months was 94路1%(95%CI 92路1-96路1); and 225 (11%) of 2126 patients received additional radiotherapy.
Treatment with six cycles of BEACOPPescalated followed by PET-guided radiotherapy was more effective in terms of freedom from treatment failure and less toxic than eight cycles of the same chemotherapy regimen. Thus, six cycles of BEACOPPescalated should be the treatment of choice for advanced stage Hodgkin's lymphoma. PET done after chemotherapy can guide the need for additional radiotherapy in this setting.
Deutsche Krebshilfe and the Swiss Federal Government.