Utility of circulating tumor DNA (ctDNA) versus tumor tissue genotyping for enrollment of patients with metastatic colorectal cancer (mCRC) to matched clinical trials: SCRUM-Japan GI-SCREEN and GOZILA combined analysis

4071 Background: We recently reported that ctDNA genotyping had advantages compared with tumor tissue testing in terms of enrollment to matched clinical trials across a wide range of GI cancers (Nakamura Y, et al. ASCO-GI 2020). Here, we investigated the utility of ctDNA genotyping in mCRC in a SCRUM-Japan GI-SCREEN and GOZILA combined analysis. Methods: In GI-SCREEN, tumor tissue genotyping was performed using a next generation sequencing (NGS)-based assay, Oncomine Comprehensive Assay since Feb 2015. In GOZILA, NGS-based ctDNA genotyping was performed using Guardant360 since Feb 2018. All tests were conducted centrally in a CLIA-certified and CAP-accredited laboratory. Patients with actionable alterations were enrolled into matched company-sponsored or investigator-initiated interventional clinical trials. Results: As of Apr 2019, 2,791 mCRC patients (2,754 eligible for analysis) in GI-SCREEN and 470 (464 eligible for analysis) in GOZILA were enrolled. There were no significant differences in baseline patient characteristics between GI-SCREEN and GOZILA. Most of trials affiliated with GI-SCREEN (81%) or GOZILA (78%) targeted the RTK/RAS/RAF pathway. Compared with tumor testing, ctDNA genotyping significantly improved turnaround time (median, 12 vs. 34 days, P < 0.0001), sequencing success rate (96.1 vs. 92.3%, P = 0.002), and detection rate of actionable alterations (73.3 vs. 62.2%, P = 0.02). Among patients with actionable alterations, enrollment to matched clinical trials was achieved in 5.0% in GI-SCREEN and 12.1% in GOZILA ( P < 0.0001). Median time from enrollment in the respective screening study to enrollment in a matched clinical trial was 6.5 months in GI-SCREEN and 0.9 months in GOZILA, respectively ( P < 0.0001). Objective response rate and progression-free survival were similar in both groups (tissue vs. ctDNA; ORR: 18.8 vs. 17.1%, P = 1.00; median PFS: 2.2 vs. 2.2 months, HR=1.05 [95% CI, 0.71–1.55], P = 0.79). Conclusions: For patients with mCRC, ctDNA genotyping had advantages over tissue genotyping with shorter turnaround time and higher sequencing success and actionable alteration detection rate, which were associated with improved clinical trial enrollment without compromising the efficacy. Funding: SCRUM-Japan Funds. Clinical trial information: UMIN000029315 .