Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496)

Abstract

Purpose: Although ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been established as the standard of care in patients with advanced Hodgkin lymphoma, newer regimens have been investigated, which have appeared superior in early phase II studies. Our aim was to determine if failure-free survival was superior in patients treated with the Stanford V regimen compared with ABVD.

Patients and methods: The Eastern Cooperative Oncology Group, along with the Cancer and Leukemia Group B, the Southwest Oncology Group, and the Canadian NCIC Clinical Trials Group, conducted this randomized phase III trial in patients with advanced Hodgkin lymphoma. Stratification factors included extent of disease (localized v extensive) and International Prognostic Factors Project Score (0 to 2 v 3 to 7). The primary end point was failure-free survival (FFS), defined as the time from random assignment to progression, relapse, or death, whichever occurred first. Overall survival, a secondary end point, was measured from random assignment to death as a result of any cause. This design provided 87% power to detect a 33% reduction in FFS hazard rate, or a difference in 5-year FFS of 64% versus 74% at two-sided .05 significance level.

Results: There was no significant difference in the overall response rate between the two arms, with complete remission and clinical complete remission rates of 73% for ABVD and 69% for Stanford V. At a median follow-up of 6.4 years, there was no difference in FFS: 74% for ABVD and 71% for Stanford V at 5 years (P = .32).

Conclusion: ABVD remains the standard of care for patients with advanced Hodgkin lymphoma.

Trial registration: ClinicalTrials.gov NCT00003389.

Fig 1.

CONSORT diagram and randomization schema of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) versus Stanford V. CT, computed tomography; IFRT, involved-field radiation therapy.

Fig 2.

(A) Failure-free (P = .32) and (B) overall survival (P = .86) are shown for all patients, showing no difference between the two arms. ABVD, doxorubicin, bleomycin, vinblastine, and dacarbazine.

Fig 3.

Patients with locally extensive disease (stage I to II bulky) were compared with patients with advanced disease (stage III to IV); patients with locally advanced disease had better (A) failure-free survival (FFS; P = .001) and (B) overall survival (OS; P = .002), but there were no differences in FFS or OS between ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and Stanford V (data not shown).

Fig 4.

In patients with low-risk disease (International Prognostic Factors Project Score [IPS], 0 to 2), there were no differences between ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and Stanford V in terms of (A) failure-free survival (FFS; P = .62) or (B) overall survival (OS; P = .08). In patients with high-risk disease (IPS, 3 to 7), there was (C) significant improvement in FFS with ABVD versus Stanford V (P = .02), but (D) no significant difference in OS (P = .15).

Fig A1.

Number of chemotherapy cycles and number of weeks of treatment for (A) ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and (B) Stanford V. In the ABVD arm, 52% of patients received six cycles (24 weeks), 54% received six to seven cycles (28 weeks), and 89% received six to eight cycles (32 weeks). In the Stanford V arm, 95% of patients received the specified 12 weeks of treatment.