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

Wednesday, March 8, 2023

3:45 PM – 3:54 PM

Location: Phoenix Convention Center, 224AB

Abstract Speaker(s)

Nicholas Fidelman, MD (he/him/his)

Professor
University Of California San Francisco

Disclosure(s): Boston Scientific: Research Grant or Support (); Merck: Research Grant or Support (); Sirtex Medical: Research Grant or Support ()

Author/Co-author(s)

CA

Chloe Atreya, MD, PhD

Associate Professor of Medicine
University of California San Francisco
MG

Madelin Griffith, BS

Senior Clinical Research Coordinator
University of California San Francisco
AM

Alexandra Milloy, BS

Senior Clinical Research Coordinator
University of California San Francisco
JC

Julia Carnevale, MD

Assistant Professor of Medicine
University of California San Francisco
AV

Alan Venook, MD

Professor of Medicine
University of California San Francisco
KV

Katherine Van Loon, MD

Associate Professor of Medicine
University of California San Francisco

Disclosure(s):

Nicholas Fidelman, MD: Boston Scientific: Research Grant or Support (); Merck: Research Grant or Support (); Sirtex Medical: Research Grant or Support ()

Purpose: Clinical efficacy of Yttrium-90 (⁹⁰Y) radioembolization (TARE) for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC) is limited by extrahepatic disease progression. TAS-102 (trifluridine and tipiracil) has overall survival benefit for patients with refractory mCRC and may be a radiosensitizer. The purpose of this study was to evaluate safety and efficacy of combination of TAS-102 and TARE for patients with chemotherapy-refractory mCRC.

Materials and Methods:

Adult patients with bilobar liver-dominant chemo-refractory mCRC were treated with sequential lobar TARE (body surface area dosimetry) using ⁹⁰Y resin microspheres in combination with TAS-102 (20mg/m², 27mg/m², and 35mg/m²) in 28-day cycles according to 3+3 dose escalation design with a 12-patient dose expansion cohort. Primary objectives were to determine maximum tolerated dose (MTD) of TAS-102 and to establish safety 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%).

Conclusion: The combination of TAS-102 and TARE for patients with liver-dominant mCRC is safe and consistently achieved disease control within the liver.