10042 Background: A large proportion of patients with advanced melanoma is not represented in phase III clinical trials, due to ineligibility. Real-world efficacy evidence of immune- and targeted therapies in these patients is lacking. We aimed to provide insight in survival outcomes of systemically treated patients who were not represented in the phase III trials in order to support clinical decision-making. Methods: Systemically treated ineligible patients with advanced melanoma diagnosed between 2014-2017 were analyzed. Prognostic importance of factors associated with overall survival (OS) was assessed by Kaplan Meier method, Cox regression models, predicted OS probabilities of prognostic subgroups and a conditional inference survival (decision) tree. Results: Of 2,536 systemically treated patients with advanced melanoma, 1,004 (40%) patients were ineligible for phase IIII trials. Ineligible patients had a poorer median OS (mOS) compared to eligible patients (8.8 vs 23 months). Eligibility criteria most strongly correlated with survival in ineligible systemically treated patients with ECOG Performance Score (PS) ≥2 vs PS 0-1 (HR 1.95 (95%CI: 1.52-2.5)), symptomatic brain metastases (BM) vs absent BM (HR 1.71 (95%CI: 1.34-2.18)) and LDH > 500 U/l vs normal (HR 1.89 (95%CI: 1.49-2.41)). All other factors for ineligibility were not associated with OS. By combining ECOG PS, BM and LDH, 18 subgroups were created. The 3-year survival probability of patients with ECOG PS ≤1, asymptomatic BM and normal LDH was 35.1%. Patients with ECOG PS of ≥2 with or without symptomatic BM had a mOS of 6.5 and 11.3 months and a 3-year survival probability of 9.3% and 23.6% respectively. In the decision tree, the covariate with the strongest predictive distinctive character for survival was LDH, followed by ECOG PS. Prognosis of LDH of > 500 U/L is infaust, although still long-term survival is possible (3-year survival probability of 15.3%). The decision tree showed the prognosis of patients with symptomatic BM can be good if ECOG PS is 0 and patients are aged ≤55 years (mOS of 22.3 months). Conclusions: Patients with advanced melanoma not represented in phase III trials treated with systemic therapy can achieve long term survival. LDH was the strongest predictive factor associated with survival, followed by ECOG PS and symptomatic BM. Other factors for ineligibility were not associated with OS. These results, together with the decision tree, can be used to provide insight in outcomes to facilitate the shared decision-making process when comparative studies are not available.