Radioembolization with Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial

Mary F. Mulcahy, Armeen Mahvash, Marc Pracht, Amir H. Montazeri, Steve Bandula, Robert C.G. Martin, Ken Herrmann, Ewan Brown, Darryl Zuckerman, Gregory Wilson, Tae You Kim, Andrew Weaver, Paul Ross, William P. Harris, Janet Graham, Jamie Mills, Alfonso Yubero Esteban, Matthew S. Johnson, Constantinos T. Sofocleous, Siddharth A. PadiaRobert J. Lewandowski, Etienne Garin, Philip Sinclair, Riad Salem*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

PURPOSE To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with secondline systemic chemotherapy for colorectal liver metastases (CLM). METHODS In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatinor irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status. RESULTS Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P 5 .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P , .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P5.0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P 5 .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity. CONCLUSION The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.

Original languageEnglish (US)
Pages (from-to)3897-3907
Number of pages11
JournalJournal of Clinical Oncology
Volume39
Issue number35
DOIs
StatePublished - Dec 10 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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