MILAN – Neither dacarbazine nor bleomycin can be safely omitted from ABVD chemotherapy without affecting efficacy in early-stage, favorable Hodgkin’s lymphoma, according to the final analysis of the German Hodgkin Study Group HD13 trial.
The primary endpoint of freedom from treatment failure (FFTF) at 5 years was 93.1% after ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, compared with 81.4% after ABV and 77.1% after AV.
All patients received two cycles of ABVD, ABV, AVD, or AV chemotherapy followed by 30 Gy involved-field radiation therapy.
"Dacarbazine cannot be omitted without considerable loss of efficacy," Dr. Karolin Behringer said at the annual congress of the European Hematology Association.
The findings confirm the inferiority of the ABV and AV arms, which were prematurely closed in 2006 and 2005 after a safety analysis detected a strong increase in events in the two arms compared with standard ABVD.
The four-armed HD13 trial, however, also sought to answer whether the AVD regimen is equivalent to ABVD chemotherapy.
The 5-year FFTF rate with AVD was 89.2%, or 3.9 percentage points lower than with ABVD (hazard ratio, 1.50; 95% confidence interval, 1.00-2.26).
This was largely due to more late relapses with AVD than with ABVD (37 vs. 20), said Dr. Behringer, of the University Hospital of Cologne, Germany.
As a result, AVD failed to meet the noninferiority test with a margin of 1.72 for hazard ratio, corresponding to a 6% difference in 5-year FFTF between ABVD and AVD.
"Bleomycin cannot be omitted with the predefined noninferiority margin of 6%," she said.
Importantly, the reduction in FFTF did not translate into poorer overall survival.
Five-year overall survival rates were 97.6% with ABVD, 94.1% with ABV, 97.6% with AVD, and 98.1% with AV, Dr. Behringer reported.
AVD patients had similar rates as those treated with ABVD chemotherapy as salvage therapy with stem cell transplantation (49% vs. 45%) or BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide, Oncovin, procarbazine, and prednisone) chemotherapy (31% vs. 35%).
Patients in the AVD arm, however, experienced significantly less grade 3/4 toxicity than did those in the ABVD arm (26.3% vs. 32.7%; P = .03). Grade 3/4 events were similar in the ABV and AV arms (28.3% vs. 26.5%), she said.
The study was conducted by the German Hodgkin Study Group. Dr. Behringer reported having no financial disclosures.