Interim Analysis of the Randomized Eortc/Lysa/Fil Intergroup H10 Trial On Early PET-Scan Driven Treatment Adaptation in Stage I/II Hodgkin Lymphoma

Abstract

Abstract Abstract 549 Introduction Early stage classical Hodgkin lymphoma (cHL) is highly curable with a combination of chemotherapy and radiotherapy (RT). Late toxicities due to RT are altering the outcome. FDG-PET (PET) has emerged as a potential new tool to early select good prognosis patients after a few cycles of chemotherapy. In the current trial, PET is used to guide early response-adapted therapy. Main objective is to evaluate whether chemotherapy alone is as effective as standard combined modality treatment in patients with an early PET negative status. In addition we evaluate whether intensification of chemotherapy is more effective than standard chemotherapy in early PET positive patients. This abstract concerns the results of the pre-planned interim safety analysis. Patients and methods All patients with a stage I and II supra-diaphragmatic cHL, between 15 and 70 years old are eligible for the study and stratified according to LYSA/EORTC criteria. Unfavorable (U) prognostic factors included patients with: CSII ≥ 4 nodal areas or age ≥ 50 yrs or MT ratio ≥ 0.35 or ESR ≥ 50 (without B-symptoms) or ESR ≥ 30 (with B-symptoms). All others are considered favorable (F). In the F group, the standard treatment is ABVDx3 and 30Gy involved-node RT (IN-RT); the early PET scan after 2 cycles is made solely for sake of comparison with the experimental arm but will not affect treatment. The experimental arm consisted of ABVDx2 followed by a PET: if the PET is negative, patients receive 2 additional cycles of ABVD and no RT. If the PET is positive, patients received BEACOPPesc x2 and 30 Gy IN-RT. In the U group, the same principles were used, the standard treatment is ABVDx4 and 30Gy IN-RT; a PET is performed for all patients after cycle 2 with no modification of treatment. The experimental arm is ABVDx2 followed by a PET: if the PET is negative, patients receive 4 additional cycles of ABVD and no RT. If the PET is positive, patients receive BEACOPPesc x2 and 30 Gy IN-RT. This report discloses the IA performed on the early PET negative patients. Results The trial opened in October 2006 and in July 2009, 1137 patients were included with a median follow-up of 1.1 years with sufficient events to allow for the planned IA. In the F early PET negative group, 188 patients were included in the standard arm, and 193 in the experimental arm. A total of 10 events occurred: one in the standard arm and nine in the experimental arm. All these events were progressions or relapses, no deaths occurred in this group. Based on the actual information fraction (10 out of the 26 events required for the final analysis) and the resulting one-sided significance level to perform the statistical test (0.102), futility was declared (p-value=0.017<0.102). The estimated hazard ratio was 9.36 (79.6% CI=[2.45–35.73]). PFS rates at one year were 100.0% and 94.9% in the standard and experimental arms respectively. In the U early PET negative group, 251 patients were included in the standard arm and 268 in the experimental arm. A total of 23 events occurred in this group: 7 in the standard arm and 16 in the experimental arm. One patient died due to toxicity without signs of progression, all remaining events were progressions or relapses. Based on the actual information fraction (23 out of the 63 events required for the final analysis) and the resulting one-sided significance level to perform the statistical test (0.098), futility was declared (p-value=0.026<0.098). The estimated hazard ratio was 2.42 (80.4% CI=[1.35–4.36]). PFS rates at one year were 97.3% and 94.7% in the standard and experimental arms respectively. The IA for the early PET positive group gave no reason for stopping this part of the trial. Final accrual was reached in June 2011 with 1950 included patients. To exclude bias caused by differences in interpretation of the early PET scans by the various central reviewers, a new blind PET review was performed on all patients with an event and an equal number of randomly selected patients without event. Six patients from this group considered negative in the first review turned positive in the new review. This did no significantly alter the outcome of the IA. Conclusion The planned futility IA of the H10 trial shows that the risk of early relapse in non-irradiated patients with stage I-II cHL was significantly higher than in standard combined modality treated patients, even in this selected group of patients with an early negative PET. Consequently, accrual was stopped for this part of the trial. Disclosures: No relevant conflicts of interest to declare.