Should unknown primary melanomas be excluded from adjuvant therapy trials? Insights from SWOG S0008.

Abstract

8517 Background: Patients (pts) with unknown primary melanoma in regional nodes are widely considered to have a better prognosis, even adjusting for other factors, so many adjuvant trials exclude these pts. Methods: 432 stage IIIB/C pts with known primary (KP) cutaneous and unknown primary (UNK) melanoma went on S0008, a randomized trial of interferon-α2b vs. biochemotherapy. Pooled data blinded to treatment were analyzed for demographics and prognosis of KPC vs UNK. Pts with KP were divided as clinically evident (macromets) versus diagnosed by sentinel node biopsy, and by time from primary diagnosis (dx) to development of nodal metastases (0-6 mos; 6 mos-5 yrs; > 5 yrs). Since UNK pts by definition had macromets, comparative analyses involved only KPC pts with macromets. Results: Of 432 pts entered onto S0008, 33 (7.6%) were UNK, while 222 had KCP macromets. Thus, 13.1% of pts with macromets were UNK. Median age (48) and number of involved nodes (2) was the same for KCP macromets and UNK pts. Overall survival (OS) was not significantly different for the two groups (p = 0.46), but relapse-free survival (RFS) was significantly better for UNK (p = 0.05). When KCP pts were subdivided by time from primary to dx of macromets, RFS was significantly worse for pts whose metastases developed 0-6 mos from dx (p = 0.008), with a trend for worse OS (p = 0.08). RFS and OS for UNK pts were identical to KPC pts where the nodal metastases developed > 6 mos after primary dx. Conclusions: In S0008, unknown primary melanoma pts had significantly better RFS but not OS than pts with macromets from known primaries. However, their outcome was similar to known primaries diagnosed > 6 mos prior to presentation with nodal metastasis. Our data strongly support the inclusion of these pts in adjuvant therapy trials and do not suggest an intrinsically better (e.g., immunologically-mediated) outcome for pts with unknown primaries. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Schering-Plough Novartis, Schering-Plough Schering-Plough