High-Dose Interferon No Benefit in Melanoma With Single Positive SLN

Adjuvant high-dose interferon alfa-2b (HDI) did not improve survival in patients with melanoma and single tumor–positive lymph nodes found using sentinel lymph node (SLN) biopsy, according to the results from the Sunbelt Melanoma Trial. In addition, HDI also did not improve survival for patients positive for disease found using reverse transcriptase polymerase chain reaction (RT-PCR) compared with observation alone.

“Although, admittedly, the Sunbelt Melanoma Trial was not adequately powered to detect small differences in disease-free survival [DFS] or overall survival [OS] and did not meet its accrual goals, there was no trend toward improvement in OS for patients treated with HDI,” wrote Kelly M. McMasters, MD, PhD, of the James Graham Brown Cancer Center at the University of Louisville, and colleagues in the Journal of Clinical Oncology.

According to background information, the Sunbelt Melanoma Trial, launched in 1997, was designed to investigate several questions related to the use of SLN biopsy and RT-PCR to screen for melanoma, as well as treatment of melanoma with HDI. The design was based in part on results from the 1996 Eastern Cooperative Oncology Group (ECOG) E1684 trial that showed that certain patients with high-risk melanoma had improved DFS and OS when treated with HDI compared with observation.

“Only a single randomized trial of HDI, ECOG E1684, which began accrual in 1984, has shown convincing and statistically significant improvement in DFS and OS,” wrote McMasters and colleagues. “These conflicting data, along with the substantial toxicity and cost associated with adjuvant HDI therapy, have done little to quell the ongoing controversy.”

The Sunbelt Melanoma Trial included patients on two protocols. In Protocol A (n = 218), patients with positive lymph nodes after SLN biopsy underwent complete lymph node dissection (CLND) and were randomly assigned to either observation or HDI. In Protocol B (n = 556), patients negative on SLN biopsy underwent staging using RT-PCR. Any patients positive after testing were randomly assigned to observation, CLND, or CLND plus HDI.

Patients in Protocol A assigned to HDI had no significant improvements in DFS (hazard ratio [HR], 0.82) or in OS (HR, 1.10) compared with patients assigned to observation alone.

“In patients with a single positive SLN, 5-year OS was 74.8% in the observation group and 71.4% in the HDI group, whereas 5-year DFS was 67.1% in the observation group and 70.9% in the HDI group,” the researchers wrote.

Similarly, in Protocol B, the researchers observed no significant differences in DFS (P = .069) or OS (P = .77) between the three treatment arms. Compared with observation, CLND alone did significantly improve DFS, but this did not translate into an improvement in OS.

“Several studies have evaluated other dosing regimens of interferon, including low and intermediate doses, as well as a pegylated formulation of interferon alfa-2b,” the researchers wrote. “A recent meta-analysis of these studies showed that interferon is associated with a significant improvement in DFS, as well as a small improvement in OS (approximately 3% absolute OS advantage; number needed to treat, 29).”

“However, this meta-analysis included ECOG E1694, which would now likely be considered inappropriate for inclusion because the GMK [ganglioside] vaccine is not equivalent to observation or placebo and did not include the results of the Sunbelt Melanoma Trial, which showed no improvement or trend for improvement in OS associated with HDI treatment. Taken together, these data support the conclusion that the benefit of HDI is small, perhaps because only a fraction of the patient population responds to the therapy,” they concluded.