Abstract 975: Genomic landscape of circulating tumor DNA in cervical cancer in Asia: NCCH1905/A-TRAIN trial
Authors: Yehgambaram Prathepamalar , Kojima Yuki , Sudo Kazuki , Yazaki Shu , Tokura Momoko , Ito Munehiro , Hoshino Mai , Fui Wong Yoke , Voon Pei Jye , Tan David SP , Lertkhachonsuk Arb-aroon , Pham Anh Tuan , Quoc Thinh Dang Huy , Ishak Wan Zamaniah Wan , Yoshida Hiroshi , Kohsaka Shinji , Nagasaka Yukari , Machida Ryunosuke , Hata Tomomi , Nakamura Kenichi , Yonemori Kan 
Published: March 2024

Background: Cervical cancer is the second most common cancer among women worldwide, with over 500,000 new cases diagnosed annually and a 50% mortality rate in Asia. The incidence and prevalence of cervical cancer is high in Asia due to limited screening, awareness of HPV infection, and access to vaccines. The purpose of this study is to evaluate the comprehensive genomic profiles of circulating tumor DNA (ctDNA) in Asian cervical cancer patients with different histological subtypes and their association with clinicopathological features.

Methods: This is an Asian multicenter prospective observational study conducted by nine institutions in Japan, Singapore, Malaysia, Thailand, and Vietnam (NCT05099978, ClinicalTrials.gov). Eligible patients had histological diagnosis of cervical cancer with metastatic or recurrent disease. Patients on chemotherapy or radiotherapy were excluded. ctDNA was analyzed in blood samples collected at newly initial diagnosis of metastatic disease and/or at disease progression. Genomic profiling was conducted by Guardant360 (Guardant Health).

Results: Ninety-nine samples from 101 cervical cancer patients were analyzed. ctDNA was detected in 70 (70.7%) samples; median time to test results was 11 days. The median number of genomic abnormalities was 1 (range, 0-22). The most frequently altered genes were PIK3CA (n=28. 28.3%), TP53 (n=18, 18.2%), KRAS (n=12, 12.1%) and STK11 (n=6, 6.1%). Clinical trial-related genomic abnormalities were detected in 59 patients (59.6%) with 40 associated with approved drugs in other indication, including those targeting PIK3CA mutation (n=28), homologous recombination deficiency (BRCA1/2, ATM and CDK12 mutation) (n=5), ERBB2 amplification (n=4) and FGFR3alterations (n=3). In squamous cell carcinoma (n=59), commonly altered genes were PIK3CA (n=21, 35.6%), TP53(n=12, 20.3%), ERBB2 (n=5, 8.5%), NOTCH1 (n=5, 8.5%) and ARID1A (n=5, 8.5%). In adenocarcinoma (n=36), commonly altered genes were KRAS (n=7, 19.4%), PIK3CA (n=6, 16.7%) and TP53 (n=5, 13.9%). The number of patients with genomic alterations relevant for clinical trials was 39 (66.1%) and 19 (52.8%) for squamous cell carcinoma and adenocarcinoma, respectively. There were no differences in the number of genomic alterations according to prior chemotherapy or radiation therapy.

Conclusion: Comprehensive genomic profiling using liquid biopsy can rapidly identify potential candidates for targeted therapy in cervical cancer patients, regardless of histopathology. Clinical studies of precision medicines in Asia are encouraged for such patients.

Citation Format: Prathepamalar Yehgambaram, Yuki Kojima, Kazuki Sudo, Shu Yazaki, Momoko Tokura, Munehiro Ito, Mai Hoshino, Wong Yoke Fui, Pei Jye Voon, David SP Tan, Arb-aroon Lertkhachonsuk, Anh Tuan Pham, Thinh Dang Huy Quoc, Wan Zamaniah Wan Ishak, Hiroshi Yoshida, Shinji Kohsaka, Yukari Nagasaka, Ryunosuke Machida, Tomomi Hata, Kenichi Nakamura, Kan Yonemori. Genomic landscape of circulating tumor DNA in cervical cancer in Asia: NCCH1905/A-TRAIN trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 975.