[ Visit Client Website ]

Before you can access ASH's online program, you must agree to the following:
  • Abstracts submitted to the ASH Annual Meeting are considered embargoed from the time of submission.
  • The media, companies and institutions issuing press releases, and others are required to abide by the embargo policies governing the Society’s annual meeting. Read ASH’s embargo policy for more information.
-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant

590 Final Analysis of a Randomized Comparison of ABVD Chemotherapy with a Strategy That Includes Radiation Therapy (RT) in Patients with Limited-Stage Hodgkin Lymphoma (HL): NCIC CTG/ECOG HD.6Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Lymphoma - Chemotherapy, excluding Pre-Clinical Models: Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma
Monday, December 12, 2011: 2:45 PM
Ballroom 20A (San Diego Convention Center)

Ralph M. Meyer, MD1, Mary Gospodarowicz, MD2*, Joseph M. Connors, MD3, Robert G Pearcey, MD4*, Woodrow A Wells, MD2*, Jane N. Winter, MD5, Sandra J. Horning, MD6, A. Rashid Dar, MD7*, Chaim Shustik, MD8, Douglas A. Stewart, MD9, Michael Crump, MD, FRCPC10, Marina S Djurfeldt, MSc11*, Bingshu E Chen, PhD12* and Lois E Shepherd, M.D.13

1Oncology, NCIC Clinical Trials Group - Queen's University, Kingston, ON, Canada
2Radiation Oncology, UHN-Princess Margaret Hospital, Toronto, ON, Canada
3British Columbia Cancer Agency, Vancouver, BC, Canada
4Radiation Oncology, Cross Cancer Institute , Edmonton, AB, Canada
5Lymphoma Committee, ECOG, Chicago, IL
6Senior VP Global Head, Clinical Dev. (Hem./Onc.), Genentech, Inc., South San Francisco, CA
7Oncology, London Health Sciences, London, ON, Canada
8Division of Haematology, McGill University Health Center, Montreal, QC, Canada
9Department of Medicine/Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada
10Princess Margaret Hospital, University Health Network, Toronto, ON, Canada
11NCIC Clinical Trials Group - Queen's University, Kingston, ON, Canada
12Community Health and Epidemiology, NCIC Clinical Trials Group - Queen's University, Kingston, ON, Canada
13Pathology and Molecular Medicine, NCIC Clinical Trials Group - Queen's University, Kingston, ON, Canada

Background: The NCIC CTG / ECOG HD.6 trial is based on the hypothesis that for patients with limited-stage HL, treatment with single-modality ABVD provides comparable disease control, is associated with a reduced incidence of deaths due to late treatment effects and thus might improve long-term survival in comparison with treatment that includes extended-field RT. In this randomized controlled phase III trial, our primary objective was to compare the 12-yr overall survivals (OS) of limited-stage HL patients treated with ABVD alone with those receiving therapy that includes RT. Secondary outcomes include freedom from disease progression (FFDP), in which those dying prior to disease progression are censored, and event-free survival (EFS), in which the first of disease progression or death is considered an event.  In 2005, we published 5-yr outcomes (median follow-up 4.2 yrs [Meyer, J Clin Oncol]). We now report results of the final analysis.

Methods: Eligible patients had non-bulky clinical stage I-IIA HL; patients with subdiaphragmatic disease were eligible if disease was confined to the iliac, inguinal and/or femoral regions. Prior to randomization, patients were stratified into low and high-risk categories; low-risk patients had all of lymphocyte predominant or nodular sclerosis histology, age < 40 yrs, ESR < 50, and involvement of 3 or fewer disease-site regions; all others were high-risk. Patients randomized to therapy that includes RT received single-modality subtotal nodal irradiation (STNI) if low-risk and combined-modality ABVD (2 cycles) plus STNI if high-risk. All patients randomized to the experimental arm received single-modality ABVD (4 cycles); those not demonstrating a complete remission with restaging after 2 cycles received 6 cycles. Between March 1994 and April 2002, 405 patients were entered; 399 were eligible and included in the primary analysis (modified intent–to-treat [ITT]). The clinical cut-off date for follow-up was 2010/DEC/31 and the database was locked on 2011/JUL/15. All P-values are 2-sided.

Results: The median duration of follow-up is 11.3 yrs. The OS was superior in patients randomized to ABVD (P=.04; HR=0.5; 12-yr estimates 94% vs. 87%). In comparison with patients randomized to therapy that includes RT, FFDP trended to being inferior in patients randomized to ABVD (P=.07; HR=1.82; 12-yr estimates 88% vs. 92%); no differences in EFS were detected (P=.5; HR=0.87; 12-yr estimates 86% vs. 80%). Sensitivity analyses included a true ITT evaluating all randomized patients and adding data obtained between the clinical cut-off and data-lock dates; results were robust and yielded similar findings.  Causes of death in ABVD vs. RT-arm patients (N = 12 vs. 24) included HL or early treatment complication (6 vs. 4), second cancers (4 vs. 9), and other (2 vs. 11).  Analysis of high-risk patients allocated to ABVD (N=137) vs. ABVD+STNI (N=139) showed similar respective results to the primary analysis: in comparison with those randomized to RT, OS was superior in the ABVD arm (12-yr estimates 92% vs. 81%; HR=.47; P=.04), FFDP was inferior (12-yr estimates 87% vs. 94%; HR=3.03; P=.01) and no differences in EFS were detected (12-yr estimates 84% vs. 78%; HR=.87; P=.6). Late-effects trended to being less frequent in ABVD patients, including second cancers (6.1% vs. 10.8%) and cardiac events (9.7% vs. 14.8%).

Conclusions: We conclude that in patients with limited-stage HL, ABVD improves OS as compared with treatment that includes STNI, including combined modality therapy, because it is associated with fewer deaths from causes other than HL. The HD.6 trial hypothesis was thus confirmed. With respect to modern RT approaches, the implications of our results are: i) at 12 years, 88% of patients are disease-free and more than 90% are alive when initially treated with ABVD alone; ii) limitations exist in using FFDP as a proxy measure for OS when late treatment effects may occur; and, iii) when treatment strategies have competing risks, long-term follow-up provides crucial insights into the interpretations of best therapy.

Disclosures: Connors: Seattle Genetics: Consultancy, Research Funding; F Hoffmann-La Roche: Research Funding. Horning: Genentech: Employment, Equity Ownership. Crump: Millennium Pharmaceuticals: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Ortho Johnson & Johnson: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

*signifies non-member of ASH