Mary F Mulcahy1, Armeen Mahvash2, Marc Pracht3, Amir H Montazeri4, Steve Bandula5, Robert C G Martin6, Ken Herrmann7, Ewan Brown8, Darryl Zuckerman9, Gregory Wilson10, Tae-You Kim11, Andrew Weaver12, Paul Ross13, William P Harris14, Janet Graham15, Jamie Mills16, Alfonso Yubero Esteban17, Matthew S Johnson18, Constantinos T Sofocleous19, Siddharth A Padia20, Robert J Lewandowski21, Etienne Garin22, Philip Sinclair23, Riad Salem21. 1. Department of Medicine, Northwestern Feinberg School of Medicine, Chicago, IL. 2. Department of Interventional Radiology, MD Anderson Cancer Center, Houston, TX. 3. Centre Eugene Marquis, Medical Oncology, Rennes, France. 4. Clatterbridge Cancer Center NHS Foundation Trust, Liverpool, United Kingdom. 5. University College London Hospital, London, United Kingdom. 6. University of Louisville, Louisville, KY. 7. Universitätsklinikum Essen, Essen, Germany. 8. Western General Hospital, Edinburgh, Scotland. 9. Yale School of Medicine, New Haven, CT. 10. The Christie NHS Foundation Trust, Manchester, United Kingdom. 11. Seoul National University, Seoul, South Korea. 12. Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. 13. Guy's Hospital, London, United Kingdom. 14. University of Washington, Seattle, WA. 15. Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom. 16. Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom. 17. Hospital Clínico Lozano Blesa, Zaragoza, Spain. 18. Indiana University School of Medicine, Indianapolis, IN. 19. Memorial Sloan Kettering Cancer Center, New York, NY. 20. University of California-Los Angeles, Los Angeles, CA. 21. Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL. 22. Centre Eugene Marquis, Nuclear Medicine, Rennes, France. 23. Boston Scientific Corporation, Marlborough, MA.
Abstract
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.
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.
Authors: Guy A van Hazel; Volker Heinemann; Navesh K Sharma; Michael P N Findlay; Jens Ricke; Marc Peeters; David Perez; Bridget A Robinson; Andrew H Strickland; Tom Ferguson; Javier Rodríguez; Hendrik Kröning; Ido Wolf; Vinod Ganju; Euan Walpole; Eveline Boucher; Thomas Tichler; Einat Shacham-Shmueli; Alex Powell; Paul Eliadis; Richard Isaacs; David Price; Fred Moeslein; Julien Taieb; Geoff Bower; Val Gebski; Mark Van Buskirk; David N Cade; Kenneth Thurston; Peter Gibbs Journal: J Clin Oncol Date: 2016-02-22 Impact factor: 44.544
Authors: Johannes Uhlig; Jelena Lukovic; Laura A Dawson; Reema A Patel; Michael J Cavnar; Hyun S Kim Journal: Am Soc Clin Oncol Educ Book Date: 2021-03
Authors: Siddharth A Padia; Guy E Johnson; Vatche G Agopian; Joseph DiNorcia; Ravi N Srinivasa; James Sayre; David S Shin Journal: J Surg Oncol Date: 2020-09-17 Impact factor: 3.454
Authors: Wilson I Gonsalves; Michelle R Mahoney; Daniel J Sargent; Garth D Nelson; Steven R Alberts; Frank A Sinicrope; Richard M Goldberg; Paul J Limburg; Stephen N Thibodeau; Axel Grothey; Joleen M Hubbard; Emily Chan; Suresh Nair; Jeffrey L Berenberg; Robert R McWilliams Journal: J Natl Cancer Inst Date: 2014-06-12 Impact factor: 13.506
Authors: Peter Gibbs; Volker Heinemann; Navesh K Sharma; Julien Taieb; Jens Ricke; Marc Peeters; Michael Findlay; Bridget Robinson; Christopher Jackson; Andrew Strickland; Val Gebski; Mark Van Buskirk; Huaqing Zhao; Guy van Hazel Journal: Clin Colorectal Cancer Date: 2018-06-12 Impact factor: 4.481
Authors: E A Eisenhauer; P Therasse; J Bogaerts; L H Schwartz; D Sargent; R Ford; J Dancey; S Arbuck; S Gwyther; M Mooney; L Rubinstein; L Shankar; L Dodd; R Kaplan; D Lacombe; J Verweij Journal: Eur J Cancer Date: 2009-01 Impact factor: 9.162
Authors: Marc Buyse; Tomasz Burzykowski; Kevin Carroll; Stefan Michiels; Daniel J Sargent; Langdon L Miller; Gary L Elfring; Jean-Pierre Pignon; Pascal Piedbois Journal: J Clin Oncol Date: 2007-11-20 Impact factor: 44.544
Authors: Mary F Mulcahy; Robert J Lewandowski; Saad M Ibrahim; Kent T Sato; Robert K Ryu; Bassel Atassi; Steven Newman; Mark Talamonti; Reed A Omary; Al Benson; Riad Salem Journal: Cancer Date: 2009-05-01 Impact factor: 6.860
Authors: Nikhil Chauhan; Mary F Mulcahy; Riad Salem; Al B Benson Iii; Eveline Boucher; Janet Bukovcan; David Cosgrove; Chantal Laframboise; Robert J Lewandowski; Fayaz Master; Bassel El-Rayes; Jonathan R Strosberg; Daniel Y Sze; Ricky A Sharma Journal: JMIR Res Protoc Date: 2019-01-17