Session Speaker

Eight Cycles Of Beacopp Escalated Compared With 4 Cycles Of Beacopp Escalated Followed By 4 Cycles Of Beacopp Baseline With Or Without Radiotherapy In Patients In Advanced Stage Hodgkin Lymphoma (HL): Final Analysis Of The Randomized HD12 Trial Of The German Hodgkin Study Group (GHSG)
Rolf-Peter Müller, Hans Theodor Eich, Volker Diehl, Andreas Engert
Germany

Purpose: The HD 12 trial of the GHSG was a multicenter four-arm randomized study: arm A was 8 x BEACOPP escalated (BE) plus 30 Gy RT, arm B was 8 x BE, arm C was 4 x BE plus 4 x BEACOPP baseline (BB) plus 30 Gy RT, arm D was 4 x BE plus 4 x BB. This study was designed to test (1) whether the BEACOPP dosage can be reduced to baseline in the last 4 cycles without loss of effectiveness, and (2) whether consolidative RT in the region of initial bulky disease (≥ 5 cm) and of residual disease (≥ 1.5 cm) is necessary following effective chemotherapy. A multidisciplinary panel reviewed all patients´ staging and restaging imaging and recommended either the continuation of therapy according to randomization, or RT independent of the randomization for patients with poor response to chemotherapy. Primary endpoint of the trial was FFTF.

Methods: Between 9/1999 and 1/2003, a total of 1.670 patients aged 16-65 were randomized. For final analysis 1.570 eligible patients were equally distributed between the 4 study arms.

Results: 97% of patients had at least one toxicity of WHO grade III or IV. Most prominent differences between pooled chemotherapy arms were anemia (65% 8BE vs 51% 4BE+4BB) and thrombopenia (65% vs 51%). Death due to acute toxicity was 3% (sepsis, cardiac, pulmonary, infection), with 20 deaths in the 8BE arms and 27 in the 4BE+4BB arms. Treatment outcome was complete remission for 92.1% of patients with another 1.7% experiencing early progression. Total progression/relapse rate was 7.8% (n=52 vs 71) with a median follow up of 78 months. OS after 5 years was 91%, 5-year FFTF was 85.4% and 5-year progression free survival (PFS) was 86.2%. Estimates for the difference at 5 years are –1.7% [-4.6%, 1.2%] for OS, –1.6% (95% CI [-5.2%, 1.9%]) for FFTF and -2.5% [-6.0%, 1.0%] for PFS. FFTF was 90% in the ‘RT’ arms A+C and 87% in the ‘no-RT’ arms B+D: Estimates for the difference FFTF at 5 years are –3.2% [-6.5%, 0.0%].

Conclusions: 4BE+4BB is clearly not significantly different from 8BE in all 3 long-term outcome parameters (p>0.19, log rank test). RT can be reduced substantially after effective chemotherapy. However, due to the irradiation of 11% of patients in the ‘no-RT’ arms due to the panel recommendation, equivalent effectiveness of a no-RT strategy cannot be proven.