Phase I Prospective Trial of TAS-102 (trifluridine and tipiracil) and Radioembolization with 90 Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases

Background: Extrahepatic disease progression limits clinical efficacy of Yttrium-90 ( 90 Y) radioembolization (TARE) for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Trifluridine and tipiracil (TAS-102) has overall survival benefit for patients with refractory mCRC and may be a radiosensitizer. Methods Sequential lobar TARE using 90 Y resin microspheres in combination with TAS-102 in 28-day cycles were used to treat adult patients with bilobar liver-dominant chemo-refractory mCRC according to 3 + 3 dose escalation design with a 12-patient dose expansion cohort. Study objectives were to establish safety and determine maximum tolerated dose (MTD) of TAS-102 in combination with TARE. Results A total of 21 patients (14 women, 7 men) with median age of 60 years were enrolled. No dose limiting toxicities were observed. Treatment related severe adverse events included cytopenias (10 patients, 48%) and radioembolization-induced liver disease (2 patients, 10%). Disease control rate in the liver lobes treated with TARE was 100%. Best observed radiographic responses were partial response for 4 patients (19%) and stable disease for 12 patients (57%). Conclusions The combination of TAS-102 and TARE for patients with liver-dominant mCRC is safe and consistently achieved disease control within the liver.