Impact of molecular testing in clinical practice in gynecologic cancers.

Tegan Hunter,Marilyn Huang,Brian Slomovitz,Matthew Schlumbrecht

doi:10.1002/cam4.2064

Abstract

BackgroundWith the growing understanding of the molecular and genetic profiles of cancers, targeted treatments are increasingly utilized in personalized cancer care. The objective of this study was to determine how these advances have translated into practice by examining how often molecular profiling of gynecological tumors led to treatment changes.MethodsWe identified women with gynecological cancers at our institution who had molecular tumor testing performed from November 2014 to June 2017. Clinicopathologic data were extracted from medical records. We determined (a) if molecular profiling identified actionable targets for which therapy is available, and (b) whether the patient's treatment course changed as a result of molecular profiling. Chi‐square, Wilcoxon rank‐sum, and Fisher's exact tests were used with a P < 0.05 considered statistically significant.ResultsWe identified 152 patients with gynecologic cancers who underwent molecular profiling. Of the 152 patients, 116 (76.3%) had actionable mutations identified, with 41 (35.3%) patients having a treatment change. Stratified by cancer type, molecular profiling most frequently identified an actionable target in patients with endometrial cancer (73.6%). Changes in treatment occurred most frequently in patients with endometrial cancer, 22 (56.4%), and ovarian cancers, 16 (39%), as compared to patients with cervical and vulvar cancer (P = 0.02). Of those patients who received a change in treatment, 39 patients (95.1%) received an FDA‐approved therapeutic agent, while two patients (4.8%) were enrolled in a clinical trial.ConclusionMolecular profiling in gynecologic cancers often identified at least one actionable mutation; however, only in a minority of these cases was the course of treatment changed. Further studies are needed to elucidate optimal timing for testing to best utilize actionable information.

Highlights

An estimated 110 000 women are expected to be diagnosed with invasive gynecological cancer in the United States in 2018, which will lead to more than 32 000 deaths.[1]
We identified 78 patients with ovarian cancer (51.3%), 46 with endometrial cancer (30.3%), 15 with cervical cancer (9.8%), 6 with uterine sarcomas (3.9%), 5 with vulvar cancers (3.3%), and two patients with gestational trophoblastic disease (GTD) (1.3%)
Precision oncology is exemplified in breast cancer with the FDA‐approved HER2‐targeting agent because HER2 amplification and overexpression are a proven predictive marker of response.[11,12]

Summary

Introduction

An estimated 110 000 women are expected to be diagnosed with invasive gynecological cancer in the United States in 2018, which will lead to more than 32 000 deaths.[1] Initial treatment for these cancers often involves a combination of surgery and chemotherapy For those who present with advanced stage disease, and for whom surgery is not curative, survival varies by tumor type. Advances in NGS, increasing throughput and quality, have decreased time and cost involved with sequencing, allowing for more genes to be sequenced.[2,3] Identification of more gene alterations allows for increased use of targeted therapies. Conclusion: Molecular profiling in gynecologic cancers often identified at least one actionable mutation; only in a minority of these cases was the course of treatment changed. Further studies are needed to elucidate optimal timing for testing to best utilize actionable information

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