Escalated BEACOPP Superior to ABDV in Early Hodgkin's Lymphoma

Zosia Chustecka

December 07, 2010

December 7, 2010 (Orlando, Florida) — Hodgkin's lymphoma is highly curable disease, and the proportion of patients who remain free from treatment failure has been increasing in recent years with the use of ever more aggressive chemotherapy regimens.

The latest of these comprises an escalated-dose regimen of BEACOPP (cyclophosphamide, doxorubicin, etoposide, procarbazine, prednisone, bleomycin, and vincristine).

The German Hodgkin Study Group has already shown that escalated (esc)BEACOPP improves outcomes in advanced Hodgkin's lymphoma, and has now demonstrated that it also does so in patients with early unfavorable Hodgkin's lymphoma (in the HD14 trial).

Final results from this study were presented here at the American Society of Hematology 52nd Annual Meeting by Andreas Engert, MD, chair of the German Hodgkin Study Group, University Hospital Cologne, Germany.

They showed that the escalated regimen is superior to the standard chemotherapy regimen of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) in terms of "overall tumor control."

However, the escalated regimen is associated with more acute toxicity, but there is no difference in overall survival, although the follow-up so far is only 5 years.

Nevertheless, Dr. Engert said that the escBEACOPP regimen should become the new standard of care in early unfavorable Hodgkin's lymphoma; it is already being used as such in new trials being conducted by the German group.

But several American experts disagreed, and said that the escBEACOPP regimen is not currently used much in the United States primarily because of concerns about toxicity.

There is currently a lot of debate about what constitutes "too much" treatment in these patients, and the very intensive chemotherapy with escBEACOPP is considered by many American oncologists to verge on "overtreatment," Andre Goy, MD, deputy director and chief of lymphoma at the John Theurer Cancer Center at Hackensack University, New Jersey, told Medscape Medical News.

ABDV has been used for 3 decades and remains the standard of care, Dr. Goy said. It has minor long-term-toxicity and it is easy to deliver, he added.

Concerns About Toxicity

The main concern with escBEACOPP is toxicity, Dr. Goy said. There is more acute toxicity and potentially more long-term toxicity; in particular, there is concern about secondary myelodysplasia, he said.

Another American clinician highlighted reproductive toxicity, noting that escBEACOPP can lead to irreversible sterility in both males and females, which is a consideration because many of these patients are of child-bearing age.

The big fears about toxicity do not fit in with the data from this trial.

Dr. Engert addressed these toxicity concerns specifically in his presentation, discussing them before the efficacy data. He acknowledged that there was more acute toxicity with the escalated regimen, but emphasized that they found no difference in later events. "The big fears about toxicity do not fit in with the data from this trial," he said.

The HD14 trial randomized 1655 patients with early unfavorable Hodgkin's lymphoma to 1 of 2 treatment groups: one group received 2 cycles of escBEACOPP, followed by 2 cycles of ABVD; the other received the current standard of 4 cycles of ABDV. After chemotherapy, all patients received 30 Gy involved-field radiation therapy. The median age of participants was 33 years.

 

The escalated regimen was associated with significantly greater acute toxicity, particularly hematological toxicity, Dr. Engert reported.

Table 1: Toxicity Reported in the HD14 Trial in Early Unfavorable Hodgkin's Lymphoma

Adverse Events escBEACOPP Therapy, % ABVD Therapy, %
Acute Grade 3/4 Toxicity 87.1 50.7
Leucopenia 79.0 24.0
Hair Loss 48.0 24.0
Thrombocytopenia 22.0 0.1
Anemia 9.0 1.0
Grade 3/4 Infections 7.3 3.4


"There was absolutely no difference with regard to treatment-related mortality, secondary malignancies, or fertility," Dr. Engert emphasized. There were 20 deaths in each group (2.5%).

He highlighted the fertility data compiled on women 40 years and younger who participated in the trial (Table 2), and in answer to a question from the audience he confirmed that all these women used their own eggs.

Table 2: Fertility Data for Women 40 Years and Younger From the HD14 Trial

Results escBEACOPP Therapy, n (%) ABVD Therapy, n (%)
No Pregnancy/Child 93 (82.0) 114 (89.0)
Pregnancy/Child 21 (18.0) 14 (11.0)
No Amenorrhea 109 (83.8) 119 (87.5)
Amenorrhea 21 (16.2) 17 (12.5)


The efficacy data show that escBEACOPP gave "better overall tumor control," Dr. Engert told meeting attendees.

The escalated regimen significantly increased the percentage of patients with an estimated 4-year freedom from treatment failure (94.7% vs 89.3%; P = .0001; hazard ratio, 2.04; 95% confidence interval, 1.39 - 2.94).

Fewer patients experienced disease progression in the escBEACOPP than in the ABDV group (0.9% vs 2.9%), and fewer had an early relapse (0.9% vs 2.8%) or a late relapse (0.9% vs 2.3%).

Dr. Engert concluded that the escBEACOPP group had a 6% progression-free survival advantage, and that progression-free survival was at "a very high level" for these patients (95.3% at 5 years).

There was no difference in overall survival, but this is not surprising because the follow-up has only been 5 years so far, he said.

Dr. Engert emphasized the superior efficacy of the escalated regimen, and concluded that "it is the new standard of care because it is significantly better in terms of tumor control."

He also suggested that now that the chemotherapy regimen is so good, attention should focus whether it is necessary it also irradiate these patients.

Will Results Change Clinical Practice?

These results are "titillating" and they have the potential to change the standard of care, said Ginna Laport, MD, associate professor of medicine, Stanford University Medical Center, California, who was moderating the press conference at which these results were highlighted. However, she pointed out that there is no overall survival difference yet, and she highlighted the greater toxicity of the BEACOPP regimen.

Most American physicians prefer to use the ABDV regimen, she said, although these latest data "will cause some to sway."

"If any study will change clinical practice, this one will," she suggested.

Dr. Engert and colleagues have disclosed no relevant financial relationships.

American Society of Hematology (ASH) 52nd Annual Meeting: Abstract 765. Presented December 6, 2010.

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