Long-term overall survival and toxicities of ABVD vs BEACOPP in advanced Hodgkin lymphoma: A pooled analysis of four randomized trials

Cancer Med. 2020 Sep;9(18):6565-6575. doi: 10.1002/cam4.3298. Epub 2020 Jul 25.

Abstract

Purpose: We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials.

Patients and methods: Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression-free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT).

Results: About 1227 patients were included. The 7-year OS was 84.3% (95% CI 80.8-87.2) for ABVD vs 87.7% (95% CI 84.5-90.2) for BEACOPP. Two follow-up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP = 1.59; 95% CI 1.09-2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7-year PFS was 71.1% (95% CI 67.1-74.6) for ABVD vs 81.1% (95% CI 77.5-84.2) for BEACOPP (P < .001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP.

Conclusions: This analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT.

Keywords: ABVD; BEACOPP; Hodgkin lymphoma; overall survival; progression-free survival; secondary cancers.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / adverse effects
  • Bleomycin / therapeutic use
  • Clinical Trials, Phase III as Topic
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Dacarbazine / adverse effects
  • Dacarbazine / therapeutic use
  • Disease Progression
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Etoposide / adverse effects
  • Etoposide / therapeutic use
  • Female
  • Hodgkin Disease / diagnosis
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / mortality
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Second Primary / etiology
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Procarbazine / adverse effects
  • Procarbazine / therapeutic use
  • Progression-Free Survival
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Stem Cell Transplantation
  • Time Factors
  • Transplantation, Autologous
  • Vinblastine / adverse effects
  • Vinblastine / therapeutic use
  • Vincristine / adverse effects
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Bleomycin
  • Procarbazine
  • Vincristine
  • Vinblastine
  • Etoposide
  • Dacarbazine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • ABVD protocol
  • BEACOPP protocol