Impact of molecular profiling on overall survival of patients with advanced ovarian cancer.

Thomas J Herzog,Matthew Powell,William Mcguire,Michael Friedlander,Andreas Voss,Sandeep Reddy,Thomas Krivak,Robert Burger,Todd Maney,Nick Xiao,David Spetzler,Ken Burnett

doi:10.18632/oncotarget.7835

Abstract

ObjectivePatients with recurrent epithelial ovarian cancer (EOC) have limited treatment options. Studies have reported that biomarker profiling may help predict patient response to available treatments. This study sought to determine the value of biomarker profiling in recurrent EOC.ResultsPatients in the Matched cohort had a median OS of 36 months compared to 27 months for patients in the Unmatched cohort (HR 0.62, 95% CI 0.41-0.96; p < 0.03). Individual biomarkers were analyzed, with TUBB3, and PGP prognostic for survival. Biomarker analysis also identified a molecular subtype (positive for at least two of the following markers: ERCC1, RRM1, TUBB3, PGP) with particularly poor overall survival.Methods224 patients from a commercial registry (NCT02678754) with stage IIIC/IV EOC at diagnosis, or restaged to IIIC/IV EOC at the time of molecular profiling, were retrospectively divided into two cohorts based on whether or not the drugs they received matched their profile recommendations. The Matched cohort received no drugs predicted to be lack-of-benefit while the Unmatched cohort received at least one drug predicted to be lack-of-benefit. Profile biomarker/drug associations were based on multiple test platforms including immunohistochemistry, fluorescent in situ hybridization and DNA sequencing.ConclusionsThis report demonstrates the ability of multi-platform molecular profiling to identify EOC patients at risk of inferior survival. It also suggests a potential beneficial role of avoidance of lack-of-benefit therapies which, when administered, resulted in decreased survival relative to patients who received only therapies predicted to be of benefit.

Highlights

Almost a quarter of a million women worldwide are diagnosed each year with epithelial ovarian cancer (EOC; including primary peritoneal and fallopian tube carcinomas) and it is the leading cause of gynecologic cancer-related death in developed countries
To evaluate the effectiveness of one such profile, we evaluated clinical data from the Caris observational Registry, whereby patient molecular profiling data were collected and coupled with clinical outcomes recorded in a central database
Of 241 eligible patients, 17 were excluded because they received no drugs after the time of tissue collection or the drugs they received were not classified by the molecular profile

Summary

Introduction

Almost a quarter of a million women worldwide are diagnosed each year with epithelial ovarian cancer (EOC; including primary peritoneal and fallopian tube carcinomas) and it is the leading cause of gynecologic cancer-related death in developed countries. The 5-year survival of EOC patients is only 44% due to the fact that 75% of women present with advanced disease [1]. 80% of advanced stage patients who www.impactjournals.com/oncotarget have residual disease after surgery and receive front-line platinum-based combination chemotherapy respond and experience a median progression free survival (PFS) of 18 months [2]. Patients who have recurrence of disease within 6 months of completion of their initial treatments have been traditionally classified as platinum-resistant. Fewer than 15% of these patients typically respond to the line of treatment and have a median survival of less than a year [3]. Most cases that are initially platinumsensitive eventually develop platinum resistance

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Conclusion