558MO - Circulating tumor (ct)DNA as a prognostic biomarker in patients (pts) with resected colorectal cancer (CRC): An updated 24 months (mos) disease free survival (DFS) analysis from GALAXY study (CIRCULATE-Japan)

Background

Postoperative ctDNA-based molecular residual disease (MRD) is reported to be associated with a high risk of recurrence. Here, we present an updated analysis on the prospective, observational GALAXY study.

Methods

Serial ctDNA was analyzed using tumor-informed assay (Signatera^TM) at 1 (4-week (wk)), 3, 6, 9, 12, 18, and 24 mos after surgery until recurrence in pts with resectable CRC. The primary endpoint was disease-free survival (DFS).

Results

Among 3,034 pts with clinical stage II-IV CRC enrolled between May 2020 and Nov 2022, 2,280 pts were included in this study. The median follow-up period was 16.5 mos (range: 0.1 - 31.9). Pts with ctDNA-positivity at 4-wk timepoint demonstrated a significantly inferior DFS compared to ctDNA-negative pts (HR: 16.9, p<0.0001). We further explored the benefit of adjuvant chemotherapy (ACT) amongst pts with stage II-III (N=1,555), in MRD-negative pts (N=1,333), 24-mo DFS was 95% in ACT group and 92.5% in no ACT group with no significant difference (HR: 1.4, p=0.2), whereas MRD-positive pts (N=222) showed significant benefit from ACT (HR: 0.4, p<0.0001) with a 24-mo DFS of 51.9% vs Not Reached. Additionally, within all stage pts who received ACT for either 3 mos or 6 mos, MRD-negative pts (N=606, HR: 1.1, p=0.89) showed no significant survival difference between the 2 cohorts while MRD-positive pts showed a significant benefit from 6 mos of ACT (N=154, HR: 0.4, p=0.002). On ctDNA dynamics analysis between 4 -12 wks, compared to pts who remained ctDNA-negative (N=941), a significantly shorter DFS was observed for pts who converted (N=22, HR: 11, p<0.001) or remained positive (N=81, HR: 20, p<0.001), respectively. Multivariate analysis in pts with stage II-III for DFS revealed that ctDNA-positivity was the most prognostic factor associated with poor outcomes (HR: 11.33, p<0.001).

Conclusions

Here we present an updated analysis on the GALAXY cohort with >2,000 pts analyzed. Our results indicate that pts with MRD-positivity showed benefit from ACT, possibly 6-mos ACT. Overall ctDNA status remains the most significant prognostic factor and predictive of pt outcomes.

Clinical trial identification

UMIN000039205.

Editorial acknowledgement

None.

Legal entity responsible for the study

The authors.

Funding

The Japan Agency for Medical Research and Development (grant 19ck0106447h0002-TY).

Disclosure

Y. Nakamura: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Guardant Health AMEA; Financial Interests, Institutional, Funding: Taiho, Chugai, Guardant Health, Genomedia, Daiichi Sankyo, Roche Diagnostics; Financial Interests, Institutional, Invited Speaker: Seagen. D. Kotani: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, MSD, Merck Biopharma, Ono pharma, Pfizer, Taiho Pharma, Takeda, Sysmex, Nihonkayaku, Novartis; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Institutional, Local PI: Ono pharma, MSD, Servier, Novartis, Janssen pharma, IQVIA, Syneos Health, CIMIC Shiftzero, CIMIC; Financial Interests, Institutional, Funding: Ono Pharma. J. Watanabe: Financial Interests, Personal, Invited Speaker: Medtronic, Johnson and Johnson, Eli Lilly, Takeda Pharmaceutical Company Limited; Financial Interests, Institutional, Funding: Medtronic, Terumo, AMCO, Stryker Japan. K. Kataoka: Financial Interests, Personal, Invited Speaker: Merck Biopharma, Eli Lilly. K. Yamazaki: Financial Interests, Personal, Invited Speaker: Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Taiho Pharmaceutical, Lilly, Sanofi, Ono Pharmaceutical, MSD, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical. K. Yeh: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, PhytoHealth, Novartis, Ono, Merck, AstraZeneca; Non-Financial Interests, Member: American Society of Clinical Oncology, American Association for Cancer Research. G. Laliotis: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc.; Non-Financial Interests, , Advisory Role: Docus, ai. V. Aushev: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc.. A. Jurdi: Financial Interests, Institutional, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera. M. Kotaka: Financial Interests, Personal, Invited Speaker: Chugai. H. Bando: Financial Interests, Institutional, Research Grant: Ono pharmaceutical; Other, Lecture fee: Ono pharmaceutical, Taiho pharmaceutical, Eli Lilly Japan. H. Taniguchi: Financial Interests, Personal, Invited Speaker: Ono, Takeda, Eli Lilly, Chugai, Taiho, Merck Biopharma; Financial Interests, Institutional, Coordinating PI: Takeda, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Ono. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Invited Speaker: Ono Pharmaceutical Co., Ltd, Sanofi K.K., Daiichi Sankyo Co., Ltd., MSD K.K., Pfizer Japan Inc., Eisai Co., Ltd.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Ono Pharmaceutical Co., Ltd., Amgen K.K., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Roche Diagnostics K.K.; Financial Interests, Personal, Research Grant: FALCO Biosystems Ltd.. E. Oki: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Bayer, Eli Lilly, Bristol Myers Squibb, MSD; Financial Interests, Personal and Institutional, Research Grant: Guardant Health. All other authors have declared no conflicts of interest.