Study Explores Risk of New Primary Melanomas After Diagnosis of Stage III/IV Melanoma in Patients Not Receiving BRAF Inhibitors
In a study reported in the Journal of Clinical Oncology, Zimmer et al assessed the incidence of spontaneous new primary melanomas in patients with stage III or IV melanoma in order to help clarify risk of BRAF inhibitor–related new melanomas. They found that patients not receiving BRAF inhibitor treatment remain at risk for further primary melanomas, with risk significantly increased in men and in patients with a history of multiple primary melanomas before or at diagnosis of stage III or IV disease.
Risk of New Primary Melanoma
The study involved 7,778 patients diagnosed with stage III or IV melanoma at Melanoma Institute Australia between 1983 and 2008 who did not receive a BRAF inhibitor. Median follow-up was 36.8 months (range, 0.1–344 months) for patients with stage III disease and 7.9 months (range, 0.03–315 months ) for the patients with stage IV disease.
At least one new primary melanoma developed in 299 (5%) of 4,215 patients with stage III melanoma and 43 (1%) of 3,563 patients with stage IV melanoma; median follow-up in patients developing new primaries was 86 months in the stage III cohort and 50 months in the stage IV cohort. The 6-month, 1-year, and 10-year cumulative incidence rates of new primary melanoma were 1.2%, 1.8%, and 5.9% after diagnosis of stage III disease and 0.2%, 0.3%, and 0.4% after diagnosis of stage IV disease.
Increased Risk
Male patients and patients with a history of multiple primary melanomas prior to or at diagnosis of stage III or IV disease were more likely to develop new melanomas after diagnosis. Men accounted for 62% of patients without new melanomas vs 76% of those with new melanomas in the stage III cohort (P < .001) and 67% vs 88% in the stage IV cohort (P = .003).
The 1-year incidence of new melanoma was 6% in patients with a history of multiple primary melanomas vs 2% in those with a single primary in the stage III cohort (P < .001) and 1% vs 0.4% in the stage IV cohort (P = .002). On multivariate competing-risks analysis, male sex (hazard ratio [HR] = 1.72, P < .001, in stage III cohort; HR = 3.71, P = .006, in stage IV cohort) and history of multiple primaries (HR = 3.19, P < .001, in stage III cohort; HR = 2.64, P = .010, in stage IV cohort) remained significant predictors of new primary melanomas among patients with stage III disease and patients with stage IV disease.
The investigators noted that development of new primary melanomas has been reported in 1.6% to 2.8% of patients over median follow-up of 10.5 to 13 months in phase III trials of BRAF inhibitors in advanced melanoma. They said that it is unclear whether this incidence reflects a drug effect or reduced dermatologic surveillance prior to the initiation of BRAF inhibitor treatment in patients with metastatic disease and outside the clinical trial setting.
The authors concluded: “Patients with stage III and stage IV melanoma remain at risk for development of further primary melanomas, particularly if they have a history of multiple primary melanomas before stage III or IV disease. The incidence rates are lower than those reported in patients receiving BRAF inhibitors. However, the results must be compared with caution because dermatologic assessment is more frequent in BRAF inhibitor trials.”
Lisa Zimmer, MD, of University Duisburg-Essen, Germany, is the corresponding author for the Journal of Clinical Oncology article.
For full disclosures of the study authors, visit jco.ascopubs.org.
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