Nine weeks of biochemotherapy effective for high-risk melanoma
Source: Skin & Allergy News, October 2014
VitalsKey clinical point: A 9-week course of biochemotherapy markedly improved relapse-free survival in high-risk melanoma, compared with standard-of-care 1-year treatment.
Major finding: The median relapse-free survival was 4.0 years for multiagent biochemotherapy, compared with only 1.9 years for high-dose interferon alone.
Data source: A phase III randomized clinical trial involving 402 patients aged 10-74 years who had high-risk melanoma and were followed for a median of 7.2 years.
Disclosures: This study was supported in part by numerous Public Health Service grants from the National Cancer Institute and by Novartis. Dr. Flaherty reported ties to Novartis and Merck, and his associates reported ties to numerous industry sources.
A 9-week course of multiagent biochemotherapy markedly improved relapse-free survival in patients with high-risk melanoma, compared with the 1-year course of high-dose interferon that has been the unchallenged standard of care for this disease for decades, according to a report published online Oct. 27 in the Journal of Clinical Oncology.
“This [phase III] randomized trial is the first to compare a multiagent regimen against high-dose interferon … and the first to demonstrate a statistically significant relapse-free survival benefit for any treatment regimen over high-dose interferon,” said Dr. Lawrence E. Flaherty of Wayne State University and the Karmanos Cancer Institute, Detroit, and his associates.
Moreover, the median relapse-free survival of 4 years achieved with biochemotherapy “represents a value not previously observed in any adjuvant therapy trial for patients with high-risk melanoma,” the investigators said. Unfortunately, this benefit did not translate into increased overall survival in this study, which was 56% at 5 years for both treatment groups.
The investigators enrolled patients aged 10-74 years (median age, 47 years) who had undergone wide excision of a cutaneous primary melanoma (stage IIIA-N2a and above) with pathologically negative margins and a complete regional lymphadenectomy. These study participants had no clinical, radiologic, or pathologic evidence of residual or metastatic melanoma, and had never undergone radiotherapy, chemotherapy, or immunotherapy for any type of cancer. They were randomly assigned to receive either high-dose intravenous interferon for 52 weeks (203 patients), or cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon every 21 days for a total of three cycles (199 patients).
After a median of 7.2 years of follow-up, the median relapse-free survival was 4.0 years for biochemotherapy, compared with only 1.9 years for high-dose interferon alone. The 5-year relapse-free survival rate was 48% for biochemotherapy, compared with only 39% for high-dose interferon alone. However, there was no corresponding improvement in overall survival: The median overall survival was 9.9 years for biochemotherapy, compared with 6.7 years for high-dose interferon alone, and 5-year overall survival was 56% for both study groups, Dr. Flaherty and his associates reported (J. Clin. Oncol. October 2014 [doi:10.1200/JCO.2013.53.1590]).
“Toxicities for biochemotherapy and high-dose interferon are different but comparable in magnitude, particularly when discontinuation for toxicity is considered,” they wrote. Biochemotherapy was associated with a higher rate of grade 4 toxicity (40% vs 7%), but rates of grade 3 and 4 toxicity were similar (76% vs 64%), and most toxicity related to biochemotherapy was hematologic and of short duration. The rate of discontinuation of treatment was 15% for biochemotherapy and 19% for high-dose interferon alone, a nonsignificant difference.