The Clinical Utility and Impact of Next Generation Sequencing in Gynecologic Cancers

SIMPLE SUMMARY: Cancer cells harbor many genetic abnormalities, but the key oncogenic pathways that lead to clinically evident cancer require driver mutations termed actionable mutations. These actionable mutations can be detected using genomic profiling or next-generation sequencing tests. This discovery has led to a tremendous change in treatment regimens from standard chemotherapy to targeted therapy where drugs are specifically targeted against these actionable mutations. Due to the cost-effectiveness and various testing platforms, utilization of these tests by oncologists has increased enormously, but the impact of targeted therapy based on these test results is still understudied. We aimed to identify the clinical utility rate of the tests and analyze the survival benefit for those receiving targeted therapy based on the test results of gynecologic cancer patients. Our findings showed high clinical utility of the tests used by gynecologic oncologists along with a significant survival benefit. ABSTRACT: Next generation sequencing (NGS) has facilitated the identification of molecularly targeted therapies. However, clinical utility is an emerging challenge. Our objective was to identify the clinical utility of NGS testing in gynecologic cancers. A retrospective review of clinico-pathologic data was performed on 299 gynecological cancers where NGS testing had been performed to identify (1) recognition of actionable targets for therapy, (2) whether the therapy changed based on the findings, and (3) the impact on survival. High grade serous carcinoma was the most common tumor (52.5%). The number of genetic alterations ranged from 0 to 25 with a mean of 2.8/case. The most altered genes were TP53, PIK3CA, BRCA1 and BRCA2. Among 299 patients, 100 had actionable alterations (79 received a targeted treatment (Group1), 29 did not receive treatment (Group 2), and there were no actionable alterations in 199 (Group3). The death rate in groups 1, 2 and 3 was 54.4%, 42.8% and 50.2%, with an average survival of 18.6, 6.6 and 10.8 months, respectively (p = 0.002). In summary, NGS testing for gynecologic cancers detected 33.4% of actionable alterations with a high clinical action rate. Along with the high clinical utility of NGS, testing also seemed to improve survival for patients who received targeted treatment.