Shotaro Matsudera1,2,3, Yoshihito Kano4, Yasuko Aoyagi4, Kohki Tohyama4, Kenta Takahashi5, Yuichi Kumaki6, Takahiro Mitsumura7, Koichiro Kimura8, Iichiro Onishi9, Akira Takemoto10, Daisuke Ban11, Hiroaki Ono11, Atsushi Kudo11, Noriko Oshima5, Kei Ogino6, Shun Watanabe12, Yukiko Tani12, Takeshi Yamaguchi12, Masanobu Nakajima12, Shinji Morita12, Satoru Yamaguchi12, Masatoshi Takagi13, Toshiaki Ishikawa6, Tsuyoshi Nakagawa6, Kentaro Okamoto6, Hiroyuki Uetake6, Minoru Tanabe11, Satoshi Miyake4, Takashi Tsuchioka12, Kazuyuki Kojima12, Sadakatsu Ikeda14,15. 1. Department of Precision Cancer Medicine, Center for Innovative Cancer Treatment, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan. matsudera.canc@tmd.ac.jp. 2. Department of Specialized Surgeries, Tokyo Medical and Dental University, Tokyo, Japan. matsudera.canc@tmd.ac.jp. 3. Department of Surgical Oncology, Graduate School of Medicine, Dokkyo Medical University, Tochigi, Japan. matsudera.canc@tmd.ac.jp. 4. Department of Precision Cancer Medicine, Center for Innovative Cancer Treatment, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan. 5. Department of Obstetrics and Gynecology, Tokyo Medical and Dental University, Tokyo, Japan. 6. Department of Specialized Surgeries, Tokyo Medical and Dental University, Tokyo, Japan. 7. Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan. 8. Department of Radiology, Tokyo Medical and Dental University, Tokyo, Japan. 9. Department of Pathology, Tokyo Medical and Dental University, Tokyo, Japan. 10. Department of Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan. 11. Department of Hepatobiliary-Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan. 12. Department of Surgical Oncology, Graduate School of Medicine, Dokkyo Medical University, Tochigi, Japan. 13. Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan. 14. Department of Precision Cancer Medicine, Center for Innovative Cancer Treatment, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan. ikeda.canc@tmd.ac.jp. 15. Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA. ikeda.canc@tmd.ac.jp.
Abstract
BACKGROUND: The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. METHODS: In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. RESULTS: Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). CONCLUSIONS: The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.
BACKGROUND: The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. METHODS: In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. RESULTS: Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). CONCLUSIONS: The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.