TY - JOUR
T1 - Radioembolization with Chemotherapy for Colorectal Liver Metastases
T2 - A Randomized, Open-Label, International, Multicenter, Phase III Trial
AU - Mulcahy, Mary F.
AU - Mahvash, Armeen
AU - Pracht, Marc
AU - Montazeri, Amir H.
AU - Bandula, Steve
AU - Martin, Robert C.G.
AU - Herrmann, Ken
AU - Brown, Ewan
AU - Zuckerman, Darryl
AU - Wilson, Gregory
AU - Kim, Tae You
AU - Weaver, Andrew
AU - Ross, Paul
AU - Harris, William P.
AU - Graham, Janet
AU - Mills, Jamie
AU - Esteban, Alfonso Yubero
AU - Johnson, Matthew S.
AU - Sofocleous, Constantinos T.
AU - Padia, Siddharth A.
AU - Lewandowski, Robert J.
AU - Garin, Etienne
AU - Sinclair, Philip
AU - Salem, Riad
N1 - Funding Information:
Supported by Boston Scientific Corporation.
Publisher Copyright:
© 2021 by American Society of Clinical Oncology.
PY - 2021/12/10
Y1 - 2021/12/10
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.21.01839
DO - 10.1200/JCO.21.01839
M3 - Article
C2 - 34541864
AN - SCOPUS:85121813461
SN - 0732-183X
VL - 39
SP - 3897
EP - 3907
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 35
ER -