Handbook of Targeted Cancer Therapy and Immunotherapy

Table 10.1: Selected prospective randomized clinical trials of ctDNA to inform clinical decision-making ( continued )

100

Clinical Trial

Description

Primary Endpoints and Results

CIRCULATE-US (NRG-GI008)

• Stage II/III MSI-S CRC postresection. If ctDNA is negative, SOC adjuvant chemo vs. observation with serial ctDNA. If ctDNA is subsequently detected, or pos itive post-op, randomized to SOC chemo or intensified mFOLFOXIRI. • Three clinical trials: • GALAXY: prospective observational trial—stage II–IV CRC amenable for curative surgery • VEGA: randomized phase III—test noninferiority of surgery alone to SOC CAPOX in HR stage II/LR stage III in ctDNA negative CRC • ALTAIR: double-blind, phase III—­

• DFS of ctDNA negative (immediate vs. delayed chemo) and ctDNA positive (SOC vs. intensified chemo) Results: Study ongoing • GALAXY: ctDNA dynamics, 6-month DFS rate • Results for GALAXY: • Improved 6-month DFS 100% vs. 45% (HR 52.3; p , 0.001) if ctDNA+ 4 weeks post-op and negative at 12 weeks, compared to remaining pos itive at 12 weeks. • 6-month DFS improved if ctDNA + and with adjuvant chemo (84%) vs. no chemo (34%, p , 0.001) • VEGA: DFS Results: Study ongoing • ALTAIR: DFS Results: Study ongoing

CIRCULATE-JAPAN

trifluridine/tipiracil vs. placebo in ctDNA-positive CRC after comple tion of adjuvant chemotherapy

Abbreviations: CRC, colorectal cancer; ctDNA, circulating tumor DNA; DFS, disease-free survival; HR, high risk; LR, low risk; MSI-S, microsatellite stable; RFS, recurrence-free survival; SOC, standard of care. a High-risk features: T4 disease, inadequate lymph node harvest ( ≤ 12), tumors complicated by obstruction or perforation, poorly differentiated, or vascular/perineural or lymphatic invasion.

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