Enabling Precision Medicine for TP53 Wild Type Endometrial Carcinoma Patients Through Validation of a Companion Diagnostic for Selinexor

Abstract

Prevalence of endometrial cancer (EC) in women has risen globally over the past several decades. EC is a major health concern due to risk factors spanning across common stages within a woman’s lifespan, such as hormonal birth control usage, pregnancy complications, obesity, aging, polycystic ovary syndrome (PCOS), tumors, chemotherapy treatment, and menopausal hormone therapy. Prognosis is poor for patients who develop advanced and recurrent EC; therefore, prompt and dynamic clinical intervention is crucial for positive patient outcomes. One such clinical intervention technique is the use of comprehensive genomic profiling (CGP) to provide molecular insight into the underlying oncogenic drivers of each individual’s unique cancer. Companion diagnostic tests utilize CGP to generate a medical data report that provides clinically actionable information about a patient’s genomic profile, enabling oncologists to develop a personalized, more targeted treatment strategy for each patient. The following research provides evidence that FoundationOne®CDx (F1CDx®), Foundation Medicine’s FDA-approved qualitative next-generation sequencing-based in vitro CGP assay for solid tumors, is a safe and reliable companion diagnostic for tumor protein p53 (TP53) wild type (WT) EC patients as a means to qualify for selinexor administration. Through analytical validation studies, F1CDx did not produce false-positive TP53 results, demonstrated reproducibility for each targeted TP53 variant with ≥95% confidence, and maintained precision in identifying TP53 alterations across differing variables. These results therefore demonstrate that F1CDx is safe and effective to facilitate improved treatment decisions for EC patients by enabling access to selinexor.