Citation: Annals of Oncology. 2019 May 31 [Epub ahead of print]
Author: Khoja L, Atenafu EG, Suciu S, Leyvraz S, Sato T, Marshall E, Keilholz U, Zimmer L, Patel SP, Piperno-Neumann S, Piulats J, Kivelä TT, Pfoehler C, Bhatia S, Huppert P, Van Iersel LBJ, De Vries IJM, Penel N, Vogl T, Cheng T, Fiorentini G, Mouriaux F, et al
Abstract: BACKGROUND: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we performed a meta-analysis using individual patient level trial data.
METHODS: Individual patient variables and survival outcomes were requested from 29 trials published from 2000-2016. Univariable and multivariable analysis were performed for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated.
RESULTS: OS data were available for 912 patients. The median PFS was 3.3 months (95%CI 2.9 to 3.6) and 6-month PFS rate was 27% (95% CI 24 to 30). Univariable analysis showed male sex, elevated (i.e. > vs ≤ upper limit of normal (ULN)) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3cm vs < 3cm) to be significantly associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH, and elevated ALP were significantly associated with shorter PFS. The most significant factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2 months (95% CI 9.5 to 11.0) and 1 year OS was 43% (95% CI 40 to 47). The most significant prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS.
CONCLUSION: Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.
© The Author 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
KEYWORDS: meta-analysis; survival benchmarks; trial design; uveal melanoma
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