Omitting Radiotherapy in Early PET-Negative Stage I/II Hodgkin Lymphoma Is Associated With Increased Risk of Early Relapse
The EORTC/LYSA/FIL Intergroup H10 trial assessed whether omitting involved-node radiotherapy would affect progression-free survival in patients with negative early positron-emission tomography (PET) scans after two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) compared with standard combined-modality treatment. As reported in the Journal of Clinical Oncology by Raemaekers et al, an interim futility analysis showing a significant excess of progression events in patients not receiving radiotherapy resulted in stopping randomization of patients with negative early PET scans.
Study Details
In the trial, patients aged 15 to 70 years with untreated clinical stage I/II Hodgkin lymphoma were classified as having favorable (n = 441) or unfavorable prognosis (n = 683) and were randomly assigned to omission of involved-node radiotherapy (experimental groups; 220 in favorable subgroup, 344 in unfavorable subgroup) or standard treatment (221 in favorable subgroup, 339 in unfavorable subgroup). Negative early PET scans after two cycles of ABVD were obtained in 193 experimental-group patients and 188 standard-group patients in the favorable subgroup (85.8% overall) and in 268 experimental-group patients and 251 standard-group patients in the unfavorable subgroup (74.8% overall).
The primary endpoint was noninferiority of progression-free survival in the experimental vs standard groups among patients with negative early PET scans. A preplanned interim futility analysis was to be performed after 12 and 22 progression events (progression, relapse, or death) occurred in the favorable and unfavorable subgroups.
Poorer Progression-Free Survival in Experimental Groups on Interim Analysis
In the favorable subgroup, nine events occurred in the experimental group vs one event in the standard group, with all events consisting of disease progression. Futility was declared, since the data showed a significant difference in progression-free survival favoring standard treatment (P = .017, less than the one-sided significance level to perform the statistical test of .102). Progression-free survival rates at 1 year were 94.9% in the experimental group and 100.0% in the standard group.
In the unfavorable subgroup, 16 events occurred in the experimental group and 9 in the standard group, with all events consisting of disease progression except for one death. Futility was declared, since the data showed a significant difference in progression-free survival favoring standard treatment (P = .026, less than the one-sided significance level to perform the statistical test). Progression-free survival at 1 year was 94.7% in the experimental group and 97.3% in the standard group.
On the basis of these findings, the independent data monitoring committee concluded it was unlikely that inferiority would be shown for the experimental arms if accrual continued to target populations and advised stopping randomization of early PET-negative patients.
The investigators concluded, “On the basis of this analysis, combined-modality treatment resulted in fewer early progressions in clinical stage I/II [Hodgkin lymphoma], although early outcome was excellent in both arms. The final analysis will reveal whether this finding is maintained over time.”
John M.M. Raemaekers, MD, PhD, of Radboud University Medical Center, Nijmegen, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Fonds Cancer, Dutch Cancer Society, Institut National du Cancer, Fondation Contre le Cancer, Assistance Publique Hopitaux Paris, and Societe Française de Medecine Nucleaire et Imagerie Moleculaire, Associazone Angela Serra, and Chugai Pharmaceutical. The study authors reported no potential conflicts of interest.
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