Abstract

The preceding trial HD9 had shown a significant superiority for escalated BEACOPP (EB) for failure-free survival (FFTF) and overall survival (OS) over COPP/ABVD or baseline BEACOPP (BB) (each 8 cycles). HD12 aimed to de-escalate chemotherapy by comparing 8 cycles EB with 4 cycles EB plus 4 cycles BB, with or without consolidatory 30 Gy radiation (RT) to initial bulky and residual disease. A total of 1661 patients aged 16–65 with HL in stage IIB (large mediastinal mass and/or E-lesions) or stage III-IV were randomised from 9/1999-1/2003 according to a factorial design between: 8EB + RT, 8EB no RT, 4EB+4BB + RT, 4EB+4BB no RT. A central diagnostic panel reviewed CT images after completion of chemotherapy independent of randomisation arm, and prescribed RT in selected cases. In the fifth analysis of HD12 (5/2006), 94% of all 1593 eligible randomised patients were evaluable, including 1498 for the chemotherapy comparison and 1449 for the radiotherapy comparison. Patient characteristics were very similar for all 4 arms. Radiation was given in arms with planned RT in 65%, in arms with no planned RT in 10%. 93% of all patients reached a complete remission, 2.2% suffered early progression, 4.6% relapsed and 8.2% died with a median folllow-up time of 48 months. Death due to acute toxicity was 3.2% (sepsis, cardiac, pulmonary, infection), with 21 such deaths in the 8EB arms and 27 in the 4EB+4BB arms. Secondary neoplasias were observed in 55 patients (3.7%): 14 AML/MDS, 12 NHL and 29 solid tumors/others. Four-year Kaplan-Meier estimates for arm pairs according to the factorial design were:

4 year rates, %(95% CI) 8EB vs. 4EB+4BB with RT vs. without RT 
FFTF 88(86–91) 86(83–89) 91(89–93) 88(86–91) 
OS 93(91–95) 91(89–93)  
4 year rates, %(95% CI) 8EB vs. 4EB+4BB with RT vs. without RT 
FFTF 88(86–91) 86(83–89) 91(89–93) 88(86–91) 
OS 93(91–95) 91(89–93)  

No significant differences were observed when comparing treatments according to the sequential analysis plan (N.B. 10% received RT in arms ‘without RT’). The final analysis, scheduled when 80% of patients have 5 years follow-up, must be awaited before final conclusions can be drawn.

Disclosure: No relevant conflicts of interest to declare.

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