US Intergroup Trial of Response-Adapted Therapy for Stage III to IV Hodgkin Lymphoma Using Early Interim Fluorodeoxyglucose-Positron Emission Tomography Imaging: Southwest Oncology Group S0816

• Authors: Oliver W. Press, Fred Hutchinson Cancer Research Center; Hongli Li, Fred Hutchinson Cancer Research Center; Heiko Schöder, Memorial Sloan Kettering Cancer Center; David J. Straus, Memorial Sloan Kettering Cancer Center; Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center; Michael LeBlanc, Fred Hutchinson Cancer Research Center; Lisa M. Rimsza, University of Arizona; Nancy L. Bartlett, Washington University School of Medicine; Andrew M. Evens, Tufts Medical Center; Erik S. Mittra, Stanford University Medical Center; Ann S. LaCasce, Dana-Farber Cancer Institute; John W. Sweetenham, Huntsman Cancer Hospital; Paul M. Barr, University of Rochester; Michelle A. Fanale, University of Texas MD Anderson Cancer Center; Michael V. Knopp, Ohio State University; Ariela Noy, Memorial Sloan Kettering Cancer Center; Eric D. Hsi, Cleveland Clinic Foundation; James R. Cook, Cleveland Clinic; Mary Lechowicz, Emory University; Randy D. Gascoyne, British Columbia Cancer Agency; John P. Leonard, Weill Cornell Medical College; Brad S. Kahl, Washington University School of Medicine; Bruce D. Cheson, Georgetown University Hospital; Richard I. Fisher, Fox Chase Cancer Center; Jonathan W. Friedberg, University of Rochester
• Journal Title: Journal of Clinical Oncology
• Volume: Volume 34, Number 17
• Publisher: American Society of Clinical Oncology | 2016-06-10, Pages 2020-+
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1200/JCO.2015.63.1119
• Subjects: Health Sciences, Oncology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; INTERNATIONAL PROGNOSTIC SCORE; CLINICAL-TRIALS; FDG-PET; ABVD; CHEMOTHERAPY; SURVIVAL; BEACOPP; DISEASE; RADIOTHERAPY; INTENSITY

Abstract

Purpose: Four US National Clinical Trials Network components (Southwest Oncology Group, Cancer and Leukemia Group B/Alliance, Eastern Cooperative Oncology Group, and the AIDS Malignancy Consortium) conducted a phase II Intergroup clinical trial that used early interim fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to determine the utility of response-adapted therapy for stage III to IV classic Hodgkin lymphoma. Patients and Methods: The Southwest Oncology Group S0816 (Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma) trial enrolled 358 HIV-negative patients between July 1, 2009, and December 2, 2012. A PET scan was performed after two initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and was labeled PET2. PET2-negative patients (Deauville score 1 to 3) received an additional four cycles of ABVD, whereas PET2-positive patients (Deauville score 4 to 5) were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for six cycles. Among 336 eligible and evaluable patients, the median age was 32 years (range, 18 to 60 years), with 52% stage III, 48% stage IV, 49% International Prognostic Score 0 to 2, and 51% score 3 to 7. Results: Three hundred thirty-six of the enrolled patients were evaluable. Central review of the interim PET2 scan was performed in 331 evaluable patients, with 271 (82%) PET2-negative and 60 (18%) PET2-positive. Of 60 eligible PET2-positive patients, 49 switched to eBEACOPP as planned and 11 declined. With a median follow-up of 39.7 months, the Kaplan-Meier estimate for 2-year overall survival was 98% (95% CI, 95% to 99%), and the 2-year estimate for progression-free survival (PFS) was 79% (95% CI, 74% to 83%). The 2-year estimate for PFS in the subset of patients who were PET2-positive after two cycles of ABVD was 64% (95% CI, 50% to 75%). Both nonhematologic and hematologic toxicities were greater in the eBEACOPP arm than in the continued ABVD arm. Conclusion: Response-adapted therapy based on interim PET imaging after two cycles of ABVD seems promising with a 2-year PFS of 64% for PET2-positive patients, which is much higher than the expected 2-year PFS of 15% to 30%.