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

Purpose: To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM).
Methods: In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or 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 = .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 P = .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 = .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.
Competing Interests: Mary F. MulcahyResearch Funding: BTG Armeen MahvashHonoraria: Sirtex MedicalConsulting or Advisory Role: Sirtex Medical, Boston Scientific, AbbiskoSpeakers' Bureau: SIR-TexResearch Funding: BTG, Sirtex MedicalTravel, Accommodations, Expenses: BTG, SIR-TexOpen Payments Link: https://openpaymentsdata.cms.gov/physician/1192235 Marc PrachtTravel, Accommodations, Expenses: MSD Steve BandulaHonoraria: Varian Medical Systems Robert C. G. MartinConsulting or Advisory Role: Angiodynamics Ken HerrmannLeadership: Sofibio, Theragnostics, Pharma15Stock and Other Ownership Interests: Sofibio, Theragnostics, Pharma15, Aktis OncologyConsulting or Advisory Role: Novartis, Bain Capital, Bayer, Advanced Accelerator Applications, Amgen, BTG, Ipsen, ITG, ROTOP Pharmaka, Siemens Healthineers, GE Healthcare Ewan BrownResearch Funding: MSD Oncology Gregory WilsonStock and Other Ownership Interests: Tandem Diabetes Care, Regeneron, Novacyt, Spire Hospital GroupConsulting or Advisory Role: Delcath Systems Paul RossStock and Other Ownership Interests: Perci Health LtdHonoraria: Sirtex Medical, Eisai, Servier, Pierre Fabre, Shire, Roche, AstraZeneca, MerckConsulting or Advisory Role: Sirtex Medical, Eisai, Servier, Roche, AstraZeneca, AmgenSpeakers' Bureau: Amgen, Merck, Servier, Boston ScientificResearch Funding: Sanofi, BayerTravel, Accommodations, Expenses: Roche, Ipsen William P. HarrisConsulting or Advisory Role: Neo Therma, Eisai, Exelixis, Bristol Myers Squibb, QED Therapeutics, Zymeworks, BD Medical, MerckResearch Funding: ArQule, Exelixis, Halozyme, Bristol Myers Squibb, MedImmune, Agios, Bayer, Merck, BTG, Boston Scientific, Koo Foundation, ZymeworksTravel, Accommodations, Expenses: Eisai Janet GrahamHonoraria: Merck Serono, Bristol Myers Squibb, Nucana, BayerConsulting or Advisory Role: Merck KGaATravel, Accommodations, Expenses: Nucana Jamie MillsTravel, Accommodations, Expenses: GenesisCare UK Matthew S. JohnsonStock and Other Ownership Interests: Endoshape, FluidXConsulting or Advisory Role: Argon Medical Devices, Boston Scientific, Cook MedicalResearch Funding: Argon Medical Devices, Boston Scientific, Black SwanExpert Testimony: Argon Medical Devices Constantinos T. SofocleousHonoraria: Ethicon/Johnson & JohnsonConsulting or Advisory Role: Varian Medical Systems, BTG, Sirtex Medical, TerumoSpeakers' Bureau: Ethicon/Johnson & JohnsonResearch Funding: BTG, Ethicon, Sirtex MedicalTravel, Accommodations, Expenses: Ethicon/Johnson & Johnson, Terumo Siddharth A. PadiaConsulting or Advisory Role: Boston Scientific, Bristol Meyer Squibb, Johnson & Johnson, Teleflex Medical, Varian Medical SystemsResearch Funding: Varian Medical Systems Robert J. LewandowskiConsulting or Advisory Role: Boston Scientific, BD Bard, Varian Medical Systems, ABKSpeakers' Bureau: Boston Scientific Etienne GarinHonoraria: BTG/Boston ScientificConsulting or Advisory Role: BTG/Boston ScientificTravel, Accommodations, Expenses: BTG/Boston Scientific Philip SinclairEmployment: Boston ScientificStock and Other Ownership Interests: Boston Scientific Riad SalemConsulting or Advisory Role: Eisai, Bard Medical, Cook Medical, Boston Scientific, Sirtex Medical, AstraZeneca, QED Therapeutics, Genentech/Roche, SiemensResearch Funding: Boston ScientificNo other potential conflicts of interest were reported.