NGS in Clinical Workflows Can Address Uterine Cancer Disparities, Study Finds

While the incidence and mortality of uterine cancer is on the rise across the board, mortality is higher for Black women. According to a study published in Gynecologic Oncology, using next-generation sequencing (NGS) may help address disparities when it is included in clinical workflows.

Some of the reasons why Black women experience higher mortality include that their cancers are often diagnosed at a later stage and with more aggressive tumors.

The researchers evaluated a workflow that implements NGS testing as part of standard care treatment for patients with gynecological malignancies; however, they limited their analysis to data from patients with uterine cancers.

The data collected are part of the Personalized Medicine Initiative, an ongoing, prospective observational cohort study at the University of Alabama in Birmingham. The study included 159 patients with advanced, recurrent, or high-risk histology uterine cancer. The majority of patients were White (67.3%) and 31.4% were Black.

Endometrial cancers are stratified into 2 categories: Type I is frequently diagnosed at earlier stages and has a favorable prognosis and type II is more aggressive, has limited response to adjuvant therapy, and is associated with a poorer prognosis. Black patients were most likely to present with type II histology. More than one-third (34.0%) had uterine papillary serous carcinoma and 14.0% had uterine carcinosarcoma. Only 22% of Black patients had endometroid, which is type I, compared with 51.4% of non-Black patients.

Black patients were also more likely to present with later-stage cancer. More than a third (38.0%) presented with stage III. However, 45.0% of non-Black patients presented with stage I disease.

Nearly all patients (89.9%) had primary surgery rather than neoadjuvant chemotherapy. Of the 136 patients with a targetable mutation, only 35.3% (n = 47) initiated a targeted therapy. The majority (61.7%) of these patients were started on mTOR inhibitors based on mutations and 72.4% of those patients were also started on the aromatase inhibitor letrozole.

The average duration of targeted therapy was 7.2 months, with 38.2% of the patients responding to the therapy for more than 6 months and 17.0% responding for longer than 12 months.

There were disparities in the initiated non–clinical trial treatments. Only 28.2% of Black patients with targetable mutations started on targeted therapy compared with 38.2% of similar non-Black patients. Less than half (45.9%) of patients overall were eligible for clinical trials based on the mutations that NGS identified, and only 20.5% were enrolled. Again, there were disparities, with 15.0% of Black patients enrolled in a clinical trial vs 22.6% of non-Black patients.

The study also found:

• The most common tumor histological subtypes were endometrioid endometrial carcinoma (EEC), serous endometrial carcinoma, and uterine carcinosarcoma.
• EEC had the largest diversity of targetable mutations.
• The most common mutations were TP53, PIK3CA, PTEN, and ARID1A.
• Black patients had a significantly higher percentage of TP53 mutations and a significant lower percentage of ARID1A mutations compared with non-Black patients.
• PIK3CA was the most common targetable mutation.
• CTNNB1 and FGFR3 was found in recurrent specimens.

Although tissue specimens from Black patients had certain mutations specific to them, they shared many of the same targetable mutations as non-Black patients.

“These findings indicate that the observed disparities for Black patients receiving targeted therapy and clinical trials cannot be explained by molecular and genetic differences,” the authors wrote.

Overall, the NGS results were obtained in 2 weeks on average and communicated to providers through the patient’s medical record. The researchers noted that NGS not only offers additional therapeutic options, but it also can be used to stratify patients to specific treatment options.

They noted that the moderate sample size of the study is one limitation. The observational nature of the study also meant the population was subject to selection bias because patients receiving NGS are more likely to have advanced stage disease or aggressive histologies.

“This initiative demonstrates the feasibility and potential impact of the integration of NGS testing into the management of uterine malignancies, illustrating how these results can provide physicians with prognostic information and targeted therapeutic options,” the authors concluded. “The potential to provide individualized treatment based on the molecular profile of the tumor increases available therapy options for patients beyond the standard of chemotherapy or radiation.”

Reference

Arend RC, Goel N, Roane BM, et al. Systematic next generation sequencing is feasible in clinical practice and identifies opportunities for targeted therapy in women with uterine cancer: results from a prospective cohort study. Gynecol Oncol. Published online August 6, 2021. doi:10.1016/j.ygyno.2021.07.017