Updated analyses from a global meta-analysis in metastatic uveal melanoma (mUM) to determine progression free and overall survival benchmarks by line of therapy: An international rare cancers initiative (IRCI) ocular melanoma study.

Abstract

9539 Background: PUMMA is an individual trial patient level meta-analysis that established survival and prognostic benchmarks in metastatic uveal melanoma (Khoja et al, 2019) in 912 patients treated 2000-2016. Methods: Herein we describe the dataset further by line of treatment to assist in establishing benchmarks of activity needed to satisfy synthetic control arm surrogates for regulatory purposes for benchmarks of PFS (Progression Free Survival) and OS (Overall Survival) in months (m). Results: Within the PUMMA dataset, 567 (62.2%) received 1st line treatment, 161 (17.7%) received 2 nd /3 rd line treatment. OS was comparable by line of treatment (P=0.2513) with 12m OS rates being 41.3% and 40.5% respectively. Median OS by line of treatment was 9.95 m (95% CI 9.23-10.74) for 1 st line and 10.15 m (7.69-11.60) for 2 nd /3 rd line. PFS was also comparable by line of treatment (p=0.51) with 12m PFS rates being 11.7% and 7.2% respectively. Median PFS by line of treatment was 2.76 m (95% CI 2.66-3.38) for 1 st line and 2.86 m (95% CI 2.73-3.52) for 2 nd /3 rd line. Multivariable analysis of the 1 st and 2 nd /3 rd line treatments separately suggested statistically significant (p<0.05) variables associated with inferior PFS in the first line setting included male sex, LDH>2X ULN, ALP>2X ULN whilst inferior PFS in the 2 nd /3 rd line was predicted by LDH>2X ULN only. Inferior OS in the 1 st line setting was statistically significantly associated with ECOG>2, Age > 65, male sex, LDH>2X ULN, ALP>2X ULN whilst inferior OS in the 2 nd /3 rd line was associated with ECOG>2, LDH>2X ULN, and ALP>2XULN. Conclusions: PUMMA continues to show value in providing benchmarks of activity for future clinical trials or regulatory purposes in mUM. The prognostic ability of LDH>2XULN retains important value across multiple lines of treatment scenarios in the PUMMA dataset.