Novel panomic validation of time to next treatment (TNT) as an effective surrogate outcome measure in 4,729 patients.

J Marshall, LS Schwartzberg, G Bepler, D Spetzler… - 2016 - ascopubs.org
J Marshall, LS Schwartzberg, G Bepler, D Spetzler, WS El-Deiry, N Xiao, SK Reddy, ES Kim…
2016ascopubs.org
11521 Background: The role of genomic and protein biomarkers in the selection of
treatments of advanced cancer is limited by the availability of outcome data following
biomarker selected treatment. TNT has been used as a clinical endpoint by the FDA and
reflects the clinical decision making process integrating efficacy and toxicity components.
We hypothesized that TNT is a meaningful surrogate endpoint correlating to overall survival
(OS) for biomarker selected treatments. Methods: We studied 4729 unselected patients …
11521
Background: The role of genomic and protein biomarkers in the selection of treatments of advanced cancer is limited by the availability of outcome data following biomarker selected treatment. TNT has been used as a clinical endpoint by the FDA and reflects the clinical decision making process integrating efficacy and toxicity components. We hypothesized that TNT is a meaningful surrogate endpoint correlating to overall survival (OS) for biomarker selected treatments. Methods: We studied 4729 unselected patients (2009-2015), heterogeneous in cancer type, stage, and line of therapy, who were referred for panomic testing utilizing IHC, PCR, ISH, NGS and RNAseq technologies. Treatment data were retrospectively obtained from the International Oncology Network database. TNT was defined as the interval between start of first treatment after tissue collection and next line of treatment. An unselected subset of 952 patients OS data was used to validate TNT as a meaningful clinical surrogate endpoint. Patients were considered “matched” (M) when the biomarker and treatment were consistent and “unmatched” (U) when they were not. The first regimen of treatment was often delivered without knowledge of biomarker results, minimizing selection bias between groups. Results: A significant improvement was observed between M (n=3011) and U (n=1718) cohorts [HR 0.85 (CI:(0.78,0.93), p<0.001)]. The median TNT was 15% longer in the M v U cohorts (248 v 215 days). Improved OS (HR of 0.69 (CI: (0.56,0.84), p<0.001)) was observed between M (n= 505) and U (n=447), with a median increase of more than 1 year (M = 1069 and U = 686 days). Conclusions: Concordance of TNT and OS for patients with biomarker-associated therapies validates the clinical utility of TNT as a surrogate endpoint that can be assessed using EMR extracted data. Additionally, this analysis demonstrates that patients receiving therapies that match their biomarker profile achieve a longer time until subsequent therapy is used. TNT reflects results of a therapeutic medical decision and thus should be further evaluated against PFS or DFI to determine the best surrogate for OS.
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