Meta-Analysis Indicates BEACOPPescalated Is Superior in Advanced Hodgkin Lymphoma
Studies evaluating two standards of care in adults with advanced Hodgkin lymphoma—ie, increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine (Matulane), and prednisone (BEACOPPescalated) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)—have not been statistically powered to test differences in overall survival. In a systematic review and network meta-analysis reported in Lancet Oncology by Nicole Skoetz of the Cochrane Haematological Malignancies Group, and colleagues, six cycles of BEACOPPescalated significantly improved overall survival compared with ABVD and other regimens.
Study Details
In this analysis, the Cochrane Library, Medline, and conference proceedings were searched for randomized controlled trials published between January 1980 and June 2013 that assessed overall survival in patients with advanced-stage Hodgkin lymphoma given BEACOPPbaseline, BEACOPPescalated, BEACOPP variants, ABVD, cyclophosphamide (mechlorethamine [Mustargen]), vincristine, procarbazine, and prednisone (C[M]OPP), hybrid or alternating chemotherapy regimens with ABVD as the backbone (eg, COPP/ABVD, MOPP/ABVD), or doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (the Stanford V regimen).
Data were pooled and a Bayesian random-effects model was used to combine direct comparisons with indirect evidence. Individual patient survival data were also reconstructed from published Kaplan-Meier curves. The primary outcome measure was overall survival.
Meta-analysis Results
A total of 2,055 records were screened and 75 papers were identified that covered 14 eligible trials assessing 11 different regimens in 9,993 patients for a total of 59,651 patient-years of follow-up. Median follow-up was 5.9 years. Between-trial heterogeneity was negligible (τ2 = 0.01).
Overall survival was greatest in patients who received six cycles of BEACOPPescalated (hazard ratio [HR] = 0.38, 95% credibility interval [CrI] = 0.20–0.75 compared with ABVD). Five-year survival was 95% with BEACOPPescalated vs 88% with ABVD (difference, 7%, 95% CrI = 3%–10%). Reconstructed individual survival data showed that BEACOPPescalated had a 10% (95% confidence interval [CI] = 3%–15%) advantage over ABVD in 5-year overall survival.
Compared with ABVD, hazard ratios (95% CrI) for overall survival were 1.40 (0.84–2.32) for MOPP, 0.98 (0.70–1.41) for MOPP/ABV, 1.19 (0.82–1.66) for C(M)OPP/ABVD, 1.07 (065–1.78) for eight cycles of BEACOPPbaseline, 0.63 (0.42–0.98) for eight cycles of BEACOPPescalated, 0.96 (0.68–1.37) for Stanford V, 1.14 (0.66–1.98) for C(M)OPP/EBV/CAD, 0.75 (0.52–1.10) for four cycles of BEACOPPescalated plus two to four cycles of BEACOPPbaseline, and 0.43 (0.22–0.86) for eight cycles of BEACOPP-14.
The investigators concluded, “Six cycles of BEACOPPescalated significantly improves overall survival compared with ABVD and other regimens, and thus we recommend this treatment strategy as standard of care for patients with access to the appropriate supportive care.”
No specific funding was provided for this project.
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