Final Results of the Sunbelt Melanoma Trial: A Multi-Institutional Prospective Randomized Phase III Study Evaluating the Role of Adjuvant High-Dose Interferon Alfa-2b and Completion Lymph Node Dissection for Patients Staged by Sentinel Lymph Node Biopsy

Abstract

Purpose: The Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy.

Patients and methods: Patients were eligible if they were age 18 to 70 years with primary cutaneous melanoma ≥ 1.0 mm Breslow thickness and underwent SLN biopsy. In Protocol A, patients with a single tumor-positive lymph node after SLN biopsy underwent CLND and were randomly assigned to observation versus HDI. In Protocol B, patients with tumor-negative SLN by standard histopathology and immunohistochemistry underwent molecular staging by reverse transcriptase polymerase chain reaction (RT-PCR). Patients positive by RT-PCR were randomly assigned to observation versus CLND versus CLND+HDI. Primary end points were disease-free survival (DFS) and overall survival (OS).

Results: In the Protocol A intention-to-treat analysis, there were no significant differences in DFS (hazard ratio, 0.82; P = .45) or OS (hazard ratio, 1.10; P = .68) for patients randomly assigned to HDI versus observation. In the Protocol B intention-to-treat analysis, there were no significant differences in overall DFS (P = .069) or OS (P = .77) across the three randomized treatment arms. Similarly, efficacy analysis (excluding patients who did not receive the assigned treatment) did not demonstrate significant differences in DFS or OS in Protocol A or Protocol B. Median follow-up time was 71 months.

Conclusion: No survival benefit for adjuvant HDI in patients with a single positive SLN was found. Among patients with tumor-negative SLN by conventional pathology but with melanoma detected in the SLN by RT-PCR, there was no OS benefit for CLND or CLND+HDI.

Fig 1.

Flow diagram of enrollment and randomization in the Sunbelt Melanoma Trial. IFN, interferon; LN, lymph node; CLND, completion lymph node dissection; RT-PCR, reverse transcriptase polymerase chain reaction; SLN, sentinel lymph node.

Fig 2.

Comparison of overall survival (A) and disease-free survival (B) in patients with a single positive sentinel lymph node randomly assigned to high-dose interferon alfa-2b adjuvant therapy (HDI) or observation.

Fig 3.

Comparison of (A) overall survival and (B) disease-free survival in patients with a sentinel lymph node positive by reverse transcriptase polymerase chain reaction only randomly assigned to observation, completion lymph node dissection (CLND), or CLND plus high-dose interferon alfa-2b (HDI) adjuvant therapy.

Fig 4.

Comparison of (A) overall survival and (B) disease-free survival in patients with sentinel lymph nodes positive by reverse transcriptase polymerase chain reaction (RT-PCR+) only randomly assigned to observation, completion lymph node dissection (CLND), or CLND plus high-dose interferon alfa-2b (HDI) adjuvant therapy, while including patients with negative sentinel lymph nodes by RT-PCR−.

Fig 5.

Subgroup analysis of Protocol A, examining differences in disease-free and overall survival in patients with a single positive sentinel lymph node randomly assigned to high-dose interferon alfa-2b adjuvant therapy (HDI) or observation.

Fig A1.

Comparison of distant disease-free survival (A) in patients with a single positive sentinel lymph node randomly assigned to high-dose interferon alfa-2b (HDI) adjuvant therapy or observation and (B) in patients with a sentinel lymph node positive by RT-PCR only randomly assigned to observation, completion lymph node dissection (CLND), or CLND+HDI.