Final analysis of the German Hodgkin Study Group (GHSG) HD14 trial concluded that intensified chemotherapy with two cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine [Matulane], and prednisone) followed by two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and 30 Gy involved-field radiotherapy (IFRT) significantly improved tumor control in patients with early unfavorable Hodgkin lymphoma. The BEACOPP plus ABVD (2+2) regimen demonstrated superior freedom from treatment failure compared with four cycles of ABVD. At 5 years, there were differences of 7.2% in freedom from treatment failure and 6.2% in progression-free survival, both favoring the 2+2 regimen over the ABVD regimen.
“The intensified 2+2 arm was clearly superior in terms of [freedom from treatment failure] and [progression-free survival], despite moderately higher acute toxicity,” investigators reported in the Journal of Clinical Oncology. There were no overall differences in treatment-related mortality or secondary malignancies.
“Patients were recruited and treated in 407 hospitals and practices in Germany, Switzerland, the Netherlands, the Czech Republic, and Austria,” the authors reported. Of the 1,528 qualified patients, more than 95% had stage II disease and the remainder had stage I disease. The median age was 32, with 9.4% older than 50 years.
“There was significantly more severe (WHO grades 3 to 4) hematologic toxicity with 2+2 (87.1%) as compared with four cycles of ABVD (50.7%); acute treatment-related mortality in the 2+2 arm was 0.52%. The more pronounced acute toxicity of 2+2 is counterbalanced by fewer relapses and fewer patients with progressive disease,” the investigators stated.
Despite the higher rate of relapse/progression in the ABVD arm, overall survival was not significantly different, because “more than 50% of relapsed or progressing patients in both arms underwent successful salvage therapy,” the authors noted. “The regimen of 2+2 plus 30 Gy [involved-field radiotherapy] is the new GHSG standard for patients with early unfavorable [Hodgkin lymphoma] age 60 years or younger,” the researchers concluded.
Both Options Reasonable
In an editorial accompanying the article, Anas Younes, MD, of MD Anderson Cancer Center in Houston, noted that “in North America, patients with bulky mediastinal stage I/II disease are typically treated with six to eight cycles of ABVD plus 36 Gy” of involved-field radiation therapy. “The HD14 study provides another option for these patients,” Dr. Younes added. “An obvious advantage for the 2+2 regimen is the shorter number of chemotherapy cycles and the use of lower doses of radiation. At the present time, there are no data to demonstrate that one approach is better than the other, and therefore, both options seem to be reasonable. It is clear that four cycles of ABVD plus 30 Gy of [involved-field radiotherapy] is not an optimal regimen for patients with bulky stage I/II disease.” ■
von Tresckow B, et al: J Clin Oncol 30:907-913, 2012.
Younes A: J Clin Oncol 30:895-896, 2012.