High-Dose BEACOPP Not Warranted for All Patients with High-Risk Hodgkin Lymphoma

Escalated bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) was reported to have similar clinical efficacy when compared with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with high-risk Hodgkin lymphoma. Patrice P. Carde, MD, PhD, of Institut Gustave Roussy, presented initial data from the European Organisation for Research and Treatment of Cancer (EORTC)–led 20012 intergroup study at Saturday’s Lymphoma Oral Abstract Session (Abstract 8002).

In the phase III study, 549 patients with exclusively high-risk stage III to IV Hodgkin lymphoma (International Prognostic Score of 3 or higher) were randomly assigned to receive eight cycles of ABVD (275 patients) or four cycles of escalated BEACOPP followed by four cycles of standard BEACOPP (274 patients). The primary endpoint of the study was event-free survival (EFS). Other endpoints included progression-free survival (PFS) and overall survival (OS). After 4 years, EFS and OS were similar in both arms of the study. EFS rates of 63.7% for ABVD and 69.3% for escalated BEACOPP were not signifi cantly different (p = 0.313); the difference in OS rates of 86.7% for ABVD and 90.3% for escalated BEACOPP were also not signifi cant (p = 0.208). Complete remission was identical in each arm of the study (83%). However, signifi cantly more patients on ABVD experienced disease progression (83.4% versus 72.8% on escalated BEACOPP; p = 0.005). Secondary malignancies and toxic deaths were similar across both arms of the study. Dr. Carde indicated that EORTC 20012 was initiated to corroborate data from the German Lymphoma Study group that demonstrated that escalated BEACOPP provided signifi cantly better clinical benefi ts than cyclophosphamide, vincristine, procarbazine, prednisone, and ABVD (COPP/ABVD) for patients with stage IIB or IIIA advanced Hodgkin lymphoma. Because ABVD is more widely recognized as standard therapy than COPP/ABVD, EORTC 20012 compared escalated BEACOPP with ABVD.

In addition, EORTC 20012 was restricted to patients with stage III or IV Hodgkin lymphoma because it was believed that if therapy with escalated BEACOPP was benefi cial, it would be more apparent in high-risk patients. Although direct comparisons cannot be made between the two studies, EORTC 20012 provides evidence that escalated BEACOPP is not signifi cantly better than standard ABVD. Dr. Carde told ASCO Daily News, “Escalated BEACOPP is tough to give, it is associated with severe neutropenia, sterility, and secondary leukemias. Data from EORTC 20012 indicate that, although it provides higher PFS, escalated BEACOPP is not warranted for all patients with advanced Hodgkin lymphoma.”

Before discussing these data, Laurie H. Sehn, MD, MPH, of the British Columbia Cancer Agency and the University of British Columbia, Canada, summarized available literature on ABVD and escalated BEACOPP in patients with advanced-stage Hodgkin lymphoma. In studies that compared the two regimens, the difference in OS was not significant for patients receiving escalated BEACOPP. She indicated that the data from EORTC 20012 were highly anticipated and concluded that “given the lack of conclusive survival benefit, routine use of BEACOPP cannot be justified.” The risk–benefit ratio for individual patients must be considered. “Current prognostic indices using clinical parameters cannot identify high-risk patients, and most patients do well with ABVD or respond to secondary therapy,” she concluded