Lawrence E Flaherty1, Megan Othus2, Michael B Atkins2, Ralph J Tuthill2, John A Thompson2, John T Vetto2, Frank G Haluska2, Alberto S Pappo2, Jeffrey A Sosman2, Bruce G Redman2, James Moon2, Antoni Ribas2, John M Kirkwood2, Vernon K Sondak2. 1. Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL. flaherty@karmanos.org. 2. Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
Abstract
PURPOSE: High-dose interferon (IFN) for 1 year (HDI) is the US Food and Drug Administration-approved adjuvant therapy for patients with high-risk melanoma. Efforts to modify IFN dose and schedule have not improved efficacy. We sought to determine whether a shorter course of biochemotherapy would be more effective. PATIENTS AND METHODS: S0008 (S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma) was an Intergroup phase III trial that enrolled high-risk patients (stage IIIA-N2a through IIIC-N3), randomly assigning them to receive either HDI or biochemotherapy consisting of dacarbazine, cisplatin, vinblastine, interleukin-2, IFN alfa-2b (IFN-α-2b) and granulocyte colony-stimulating factor given every 21 days for three cycles. Coprimary end points were relapse-free survival (RFS) and overall survival (OS). RESULTS: In all, 432 patients were enrolled. Grade 3 and 4 adverse events occurred in 57% and 7% of HDI patients and 36% and 40% of biochemotherapy patients, respectively. At a median follow-up of 7.2 years, biochemotherapy improved RFS (hazard ratio [HR], 0.75; 95% CI, 0.58 to 0.97; P = .015), with a median RFS of 4.0 years (95% CI, 1.9 years to not reached [NR]) versus 1.9 years for HDI (95% CI, 1.2 to 2.8 years) and a 5-year RFS of 48% versus 39%. Median OS was not different (HR, 0.98; 95% CI, 0.74 to 1.31; P = .55), with a median OS of 9.9 years (95% CI, 4.62 years to NR) for biochemotherapy versus 6.7 years (95% CI, 4.5 years to NR) for HDI and a 5-year OS of 56% for both arms. CONCLUSION:Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in RFS but no difference in OS and more toxicity compared with HDI.
RCT Entities:
PURPOSE: High-dose interferon (IFN) for 1 year (HDI) is the US Food and Drug Administration-approved adjuvant therapy for patients with high-risk melanoma. Efforts to modify IFN dose and schedule have not improved efficacy. We sought to determine whether a shorter course of biochemotherapy would be more effective. PATIENTS AND METHODS: S0008 (S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma) was an Intergroup phase III trial that enrolled high-risk patients (stage IIIA-N2a through IIIC-N3), randomly assigning them to receive either HDI or biochemotherapy consisting of dacarbazine, cisplatin, vinblastine, interleukin-2, IFN alfa-2b (IFN-α-2b) and granulocyte colony-stimulating factor given every 21 days for three cycles. Coprimary end points were relapse-free survival (RFS) and overall survival (OS). RESULTS: In all, 432 patients were enrolled. Grade 3 and 4 adverse events occurred in 57% and 7% of HDI patients and 36% and 40% of biochemotherapy patients, respectively. At a median follow-up of 7.2 years, biochemotherapy improved RFS (hazard ratio [HR], 0.75; 95% CI, 0.58 to 0.97; P = .015), with a median RFS of 4.0 years (95% CI, 1.9 years to not reached [NR]) versus 1.9 years for HDI (95% CI, 1.2 to 2.8 years) and a 5-year RFS of 48% versus 39%. Median OS was not different (HR, 0.98; 95% CI, 0.74 to 1.31; P = .55), with a median OS of 9.9 years (95% CI, 4.62 years to NR) for biochemotherapy versus 6.7 years (95% CI, 4.5 years to NR) for HDI and a 5-year OS of 56% for both arms. CONCLUSION: Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in RFS but no difference in OS and more toxicity compared with HDI.
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