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Stage III, IV melanoma increased risk for new primary melanomas
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Patients with stage III or IV melanoma were at increased risk for developing new primary melanomas, according to study results.
The association was particularly apparent among men, as well as patients with a history of multiple primary melanomas before stage III or IV disease.
The analysis included 4,215 patients with stage III melanoma and 3,563 patients with stage IV melanoma who were diagnosed between 1983 and 2008 at the Melanoma Institute Australia.
Among patients with stage III disease, 229 (5%) had at least one new primary melanoma after their initial diagnosis.
The 6-month cumulative incidence rate of developing a new primary melanoma in this patient population was 1.2% (95% CI, 0.86-1.51). This increased to 1.8% (95% CI, 1.44-2.26) at 1 year, and 5.9% (95% CI, 5.08-6.74) at 10 years.
Among patients with stage IV disease, 43 (1%) had at least one new primary melanoma.
The cumulative incidence rate among these patients was 0.2% (95% CI, 0.07-0.36) at 3 months, 0.3% (95% CI, 0.15-0.51) at 6 months and 0.4% (95% CI, 0.25-0.7) at 1 year.
The risk for new primary melanomas was increased in men with stage III (HR=1.72; 95% CI, 1.28-2.32) and stage IV (HR=3.71; 95% CI, 1.46-9.44) disease.
Patients with a prior history of multiple primary melanoma also were at increased risk (stage III, HR=3.19; 95% CI, 2.24-4.52; stage IV, HR=2.64; 95% CI, 1.27-5.52).
“Whether patients with stage IV melanoma should undergo surveillance for new primary melanomas remains arguable at this point in time because of improved, but still poor, OS in this patient cohort,” the researchers wrote. “Although the incidence rates are lower than those observed in the studies of dabrafenib (Tafinlar, GlaxoSmithKline) and vemurafenib (Zelboraf, Genentech), the results must be compared with caution because of the more frequent and thorough dermatologic assessments in the BRAF inhibitor studies.”
Disclosure: The researchers report consultant or advisory roles with, as well as honoraria, research funding or other remuneration from, Abbot Molecular, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Morphotek, Novartis and Roche.
Perspective
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John Kirkwood, MD
Zimmer and colleagues report the incidence of new primary melanoma among patients with a prior history of melanoma from the vantage of the Melanoma Institute of Australia’s Sydney Melanoma Unit database, a large experience that harks to the pioneering work of Prof. Gerald Milton and his colleagues in the 1970s. The assessment of the basal risk in this series will potentially serve as a reference point for future evaluation of the influence BRAF and other signaling inhibitors — not to mention immunomodulators like ipilimumab (Yervoy, Bristol-Myers Squibb) and newer anti-PD–1 agents. The influence of new therapies active against advanced disease upon the incidence of new primary melanoma is a long-overlooked area, and the factors that augur for improved RFS or OS of resectable disease (with adjuvant therapy) or treatment of metastatic melanoma (with advanced-disease therapy) may differ from the factors that influence the progression and early transformation of melanocytic precursors. The etiopathology of primary melanoma — and its non-obligate precursors and risk markers like atypical nevi — needs considerably more work to answer this question. The influence of agents previously utilized for therapy of advanced and high-risk melanoma upon the precursor lesions has only been studied in relation to the interferons (Wang W. Clin Cancer Res. 2007;13:1523-1531; Wang W. J Invest Dermatol. 2008;128:1997-2002. Wang W. Cancer Immunol Immunother. 2008;57:1315-1321.). The Zimmer study gives us a solid reference point for the assessment of future patients with stage III and IV melanoma: The risk of new primary melanoma among 5,963 patients with prior stage III or stage IV disease shows — not surprisingly — that patients with a prior history of multiple primary melanomas have the highest risk. It will be of interest to learn whether there is any suggestion of an impact of current molecular interventions, as well as whether immunomodulatory therapy with the checkpoint inhibitors for CTLA4 and PD-1 may influence this risk of new primary melanoma among patients with stage III or IV melanoma.
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