Tumor fraction to improve patient selection for oncology early phase clinical trials: Analysis of two precision medicine studies.

Abstract

3005 Background: Typical entry criteria in early phase studies include expected life expectancy greater than 3 months. However, this evaluation is quite subjective and more objective and reproducible tools are needed to improve patients (pts) selection. The quantification of ctDNA shed by measuring tumor fraction (TF) has been associated with prognosis in solid tumors pts. However, prognostic implications of TF quantification have been evaluated primarily in retrospective studies and in a limited number of cancer types. We report here the first prospective evaluation of the prognostic impact of TF in 2 independent precision medicine studies enrolling pts referred to consider their eligibility to early phase trials. Methods: All consecutive adult pts with an advanced solid tumor included between December 2020 and December 2021 in 2 precision medicine studies: BIP (NCT02534649, sponsor: Institut Bergonié, Bordeaux, France) and STING (NCT04932525, sponsor: Institut Gustave Roussy, Villejuif, France). All pts underwent comprehensive genomic profiling with the 324-gene FoundationOne. TF was analyzed as a binary variable, indicating whether a specimen had TF ≥10% or TF <10%. Multivariate analysis included previously validated prognostic scores: the Royal Marsden Hospital (albumin, LDH, number of metastatic sites) and the GRIm (LDH, neutrophil/lymphocyte ratio (NLR), albumin) scores as well as their individual components. Results: 1912 pts: N=965 in BIP and N=947 in STING were included. Their characteristics are described. High TF was associated with significantly worse overall survival (OS) in both BIP and STING studies. On multivariate analysis, TF was associated with worse OS (HR:2.49 [CI95%: 2.11 - 2.95, p<0.001] and HR:2.52 [CI95%: 2.06 - 3.08, p<0.001] in BIP and STING studies respectively) independently of the RMH and GRIM scores as well as their individual components. Conclusions: This is the first prospective analysis confirming that TF is a strong prognostic factor in pts with advanced solid tumors and represent an helpful tool in the process of patient selection for phase I trial entry. [Table: see text]