Unknown Primary Tumor High-Risk Melanoma As A Unique Patient Population With Distinct Prognosis In The Adjuvant Setting: An Ecog-Acrin E1609 Study Analysis.

e22090 Background: E1609 enrolled 1670 adult patients (pts) with resected AJCC7 stages IIIB, IIIC, M1a, M1b melanoma and compared adjuvant ipilimumab at 3 or 10 mg/kg (ipi3 and ipi10) to high dose interferon-alfa (HDI). With over 5 years of follow up, the risk of relapse and death by primary tumor status and by stage group is expected to inform the design of future adjuvant trials and ultimately, clinical practice. Methods: Unknown primary melanoma status was defined as initial presentation with cutaneous, nodal or lung metastasis that was completely resected without a history of known primary melanoma. We evaluated the pt distribution by the initial site of metastasis. Further, we evaluated the risk of relapse and death by primary tumor status and by stage group. Five-year relapse-free survival (RFS) and overall survival (OS) rates and 95% CIs were estimated by Kaplan-Meier method. Stratified (by stage) log-rank test was used to compare RFS and OS by primary tumor status. Two-sided p-values were derived. Results: Unknown primary melanoma represented 12.8% of the total study population including 11.7% on the ipi arms and 14.7% on HDI. Site of metastasis at initial presentation among unknown primary cases included cutaneous and nodal (97%) and lung (3%). Among the overall study population, M1a stage group included the highest proportion of pts with unknown primary (42.2%). Stratifying by stage, RFS (p = 0.001) and OS (p = 0.009) were significantly better for pts with unknown primary compared to known primary. Including only ipi3 and ipi10 pts, RFS (p = 0.005) and OS (p = 0.023) were consistently significantly better in favor of unknown primary. Five-year RFS and OS rates by primary tumor status and stage group among pts treated with ipi (ipi3 and ipi10) are summarized in Table. Conclusions: Unknown primary status represents a unique population among high-risk melanoma pts treated with ipi with improved RFS and OS outcomes that support their separate assessment in future immunotherapy adjuvant trials. In-depth analyses of the tumor biology and host immunology are ongoing. Outcome analyses by the overall study stage groups and the HDI arm will be reported at the meeting. Clinical trial information: NCT01274338. [Table: see text]