The international, randomized phase 3 HD15 trial established 6xeBEACOPP as standard therapy for patients with newly diagnosed advanced-stage Hodgkin lymphoma (HL) within the German Hodgkin Study Group (GHSG). We performed a follow-up analysis to assess long-term efficacy and safety of this approach. Between 2003 and 2008, 2182 patients aged 18 to 60 years were recruited and randomized in a 1:1:1 ratio between 8 or 6 cycles of eBEACOPP or 8 cycles of the dose-dense BEACOPP-14 regimen, each followed by 30 Gy radiotherapy in case of positron emission tomography (PET)-positive residual lesions ≥2.5 cm. The study aimed at demonstrating non-inferiority regarding efficacy of the 2 experimental arms on a significance level of 2.5% each. The intention-to-treat analysis comprised 2126 patients with a median follow-up of 102 months. Ten-year progression-free survival was 81% (97.5% CI 77–85) with 8xeBEACOPP, 84% (80–87) with 6xeBEACOPP, and 84% (80–87) with 8xBEACOPP-14; the non-inferiority margin of 1.51 for the hazard ratio (HR) could be excluded for both comparisons (6xeBEACOPP, HR = 0.7, 97.5% CI 0.5–1.0; 8xBEACOPP-14, HR = 0.9, 97.5% CI 0.7–1.2). Overall survival at 10 years was 88% (85–91), 90% (88–93), and 92% (89–94), respectively. A total of 142 second malignancies corresponding to 10-year cumulative incidences of 10%, 7%, and 7% and standardized incidence ratios of 4.3, 2.5, and 2.8 were reported for 8xeBEACOPP, 6xeBEACOPP, and 8xBEACOPP-14, respectively. This updated analysis of the HD15 trial thus confirms the efficacy and reports on the long-term safety of a shortened first-line chemotherapy consisting of 6xeBEACOPP followed by PET-guided radiotherapy in advanced-stage HL.
1German Hodgkin Study Group (GHSG), Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany
2Department of Internal Medicine—Hematology, University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic
3Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland
4Department of Medical Oncology, University Hospital, Inselspital, Bern, Switzerland
5University of Heidelberg, Heidelberg, Germany
6VU University Medical Center, Amsterdam, The Netherlands
7Department of Internal Medicine—Haemato-Oncology, University Hospital and Faculty of Medicine of Masaryk University, Brno, Czech Republic
8University of Tübingen, Tübingen, Germany
9IIIrd Medical Department, Paracelsus Medical University and Salzburg Cancer Research Institute, Salzburg, Austria
10Salzburg Cancer Research Institute and AGMT (Arbeitsgemeinschaft Medikamentöse Tumortherapie), Salzburg, Austria
11Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany
12Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany
13Berlin Reference Center for Lymphoma and Haematopathology, Berlin, Germany.
Correspondence: Andreas Engert, German Hodgkin Study Group (GHSG), Department of Internal Medicine I, University Hospital of Cologne, Kerpener Str. 62, D-50924 Cologne, Germany (e-mail: email@example.com).
Funding/support: The study has been supported by the Deutsche Krebshilfe e.V. (German Cancer Aid) and the Swiss State Secretariat for Education, Research and Innovation (SERI).
Trial registration: The HD15 trial was registered with Current Controlled Trials, number ISRCTN32443041.
Author contributions: AE, JM, TP, JM, JMZ, ZK, DAE, MS and RG directed clinical activities at participating study centers. HS led the reference pathology. HE, CK, MD and MF did the central PET review. HG led the statistical analyses of the data. MF directed activities at the GHSG central office. AE, VD, and PB led the design of the study protocol. AE is the principal investigator of the study. AE and HG wrote the first draft of the report. All authors contributed to data interpretation, reviewed the draft, and approved the final version of this report.
Disclosure: The Deutsche Krebshilfe reviewed the trial protocol for adherence to good clinical practice. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data and the corresponding author had final responsibility for the decision to submit for publication. The authors have indicated they have no potential conflicts of interest to disclose.
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Received October 4, 2017
Accepted October 25, 2017