RWD73 THE SOCIO-ECONOMIC BURDEN OF END-STAGE KIDNEY DISEASE: REAL-WORLD EVIDENCE FROM BULGARIA

Objectives: This research aims to compare overall (OS) and progression-free (PFS) survival between mono anti-PD1 and mono BRAF-inhibitors (monoBRAFi) or combination of BRAF-and MEK-inhibitors (BRAFi+MEKi) in the first line therapy of patients with BRAFV600-mutated advanced melanoma in the routine clinical practice.Methods: Data on anti-PD1 drug prolgolimab and different options of BRAFi6MEKi were obtained from observational studies FORA (NCT05120024) and ADMIRE (NCT03663647), respectively.115 patients on prolgolimab, 130 on BRAFi +MEKi, 76 on monoBRAFi were included into this analysis.Due to non-proportionality of hazards for OS and PFS a difference in the restricted mean survival time (rmstD) over 30 months was used as an estimand.Marginal RMST was assessed as an area under a Kaplan-Meier curve adjusted to the inverse probability of treatment weights (IPTW) computed from propensity scores.Covariates for the latter included sex, age, M-stage, ECOG, LDH level.Preliminary multiple imputation of missings in ECOG and LDH level was done.IPTW-adjusted rmstDs with bootstrapped standard errors from 50 imputed datasets were pooled according to the Rubin's rules.Sensitivity analyses to missings not at random (MNAR) and unobserved confounders were conducted.Results: Averaged over imputations, effective sample size (ESS) for prolgolimab, BRAFi+MEKi and monoBRAFi was 79/115 (68.7%), 102/ 130 (78.5%), 61/76 (80.3%) patients, accordingly.On prolgolimab IPTW-adjusted 30month rmstD compared to monoBRAFi and BRAFi+MEKi was 2.9 (95% CI, -0.4,6.2, p=0.085) and 0.8 (95% CI, -2.0, 3.6, p=0.566) months for OS and 4.0 (95% CI, 0.5, 7.8, p=0.027) and 0.9 (95% CI, -2.6, 4.5, p=0.597) months for PFS, respectively.Estimates were almost insensitive to MNAR and moderately sensitive to unobservables.Conclusions: Due to high population heterogeneity, small ESS and non-proportionality of hazards, further analysis on the long-term data is necessary for more precise estimates of differences in survival between anti-PD1 and targeted therapies for adults with BRAFV600-mutated advanced melanoma in the routine clinical practice.