Impact of molecular testing in clinical practice in gynecologic cancers

Abstract

Background With 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. Methods We 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. Results We 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. Conclusion Molecular 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.

Unique Molecular Features in High-Risk Histology Endometrial Cancers

“…These are considered actionable targets because the identified molecular feature (i.e., the target) in a tumor has a specific therapy (i.e., the action) that works against tumors with that molecular feature. These genetic changes, known as actionable targets, are typically identified by next-generation sequencing of tumors or molecular immunohistochemistry (i.e., progesterone receptor, HER2) [67]. The Figure summarizes some of the more promising actionable targets and their specific therapies.…”

“…After the discovery of actionable targets, treatment plans were changed in 56% of women with endometrial cancer. Most of the targeted therapies involved hormonal therapy (i.e., tamoxifen, letrozole, or medroxyprogesterone acetate) or mTOR inhibition (i.e., everolimus or temsirolimus) [67]. The frequency of actionable mutations was similar to the frequency of actionable mutations in ovarian cancer.…”

“…Endometrial cancer guidelines do not yet recommend this technology. However, this study highlights the fact that endometrial cancers have as many actionable targets identified that clinically change therapy and should be studied further [67].…”

GYNOCARE Update: Modern Strategies to Improve Diagnosis and Treatment of Rare Gynecologic Tumors—Current Challenges and Future Directions

“…As the majority of individual molecular alterations identified so far do not have an ad-hoc FDA-or EMA-approved therapy, the need for larger studies employing high-throughput technologies for molecular testing, to better define the cancer-related aberration, is clearly warranted. However, there is still much to be learnt on the optimal timing of testing and incorporation into clinical practice [ 29 ].…”

“…Now, when standard of care options fail, molecular testing such as next generation sequencing (NGS), Sanger sequencing and pyrosequencing, is increasingly utilized to identify targeted therapies for cancer treatments such as hormone therapies, pathway specific therapies, and immunotherapies. Molecular testing can identify opportunities for drugs approved by regulatory agencies as well as experimental therapeutics in clinical trials [ 29 ]. Thus, regarding RGT, it will be necessary to evaluate how the findings coming from the application of High-Throughput technologies (e.g., NGS, proteomics and other molecular testing) could lead to effective clinical actions, through the identification of predictive biomarkers useful both in disease prediction and in its clinical follow-up, by means of a pharmacogenomics approach.…”