Belinda Lee1,2,3, Hui-Li Wong1,2,3, Mark Tacey3,4, Jeanne Tie1,2,5, Rachel Wong1,6,7, Margaret Lee1,2,6, Louise Nott8, Jeremy Shapiro7,9, Ross Jennens10, Natalie Turner1,2, Ben Tran1,2, Sumitra Ananda5, Desmond Yip11, Gary Richardson9, Phillip Parente6,7, Lionel Lim6, Greg Stefanou12, Matthew Burge13, Mahesh Iddawela14, Jeremy Power15, Peter Gibbs1,2,3,5. 1. Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia. 2. Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia. 3. Faculty of Medicine, Dentistry & Health Sciences University of Melbourne, Melbourne, VIC, Australia. 4. Melbourne EpiCenter, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia. 5. Western Health, Department of Medical Oncology, Boxhill, TAS, Australia. 6. Eastern Health, Department of Medical Oncology, Boxhill, TAS, Australia. 7. Monash University, Department of Medicine, Nursing and Health Sciences, Hobart, TAS, Australia. 8. Royal Hobart Hospital, Department of Medical Oncology, Hobart, TAS, Australia. 9. Cabrini Health, Department of Medical Oncology, Malvern, VIC, Australia. 10. Epworth Hospital, Department of Medical Oncology, Richmond, VIC, Australia. 11. Canberra and Calvary Hospitals, Department of Medical Oncology, Garran, ACT, Australia. 12. John Fawkner Hospital, Department of Medical Oncology, Coburg, VIC, Australia. 13. Royal Brisbane Hospital, Department of Medical Oncology, Brisbane, QLD, Australia. 14. Goulburn Valley Health, Department of Medical Oncology, Shepparton, VIC, Australia. 15. Launceston General Hospital, Department of Medical Oncology, Launceston, TAS, Australia.
Abstract
BACKGROUND: Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood. METHODS: Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT. Progression-free survival (PFS), overall survival (OS) and safety endpoints were analyzed. RESULTS: Of 1204 mCRC patients, 826 (69%) were eligible for inclusion. Bevacizumab use was similar in both arms (IPT (64%) versus RPT (70%)); compared with chemotherapy alone, bevacizumab use was associated with significantly longer PFS (IPT: 8.5 months vs 4.7 months, P = 0.017; RPT: 10.8 months vs 5.8 months, P < 0.001) and OS (IPT: 20 months vs 14.8 months, P = 0.005; RPT: 24.4 months vs 17.3 months, P = 0.004)).1 Bevacizumab use in an IPT was associated with more GI perforations (4.5% vs 1.8%, P = 0.210) but less frequent bleeding (1.5% vs 5.3%, P = 0.050) and thrombosis (1.5% vs 2.7%, P = 0.470), versus chemotherapy alone. Median survival was equivalent between patients that did or did not experience bevacizumab-related adverse events - 20.0 months versus 19.9 months, hazard ratio = 0.98, P = 0.623.1 CONCLUSIONS: The addition of bevacizumab significantly improved survival outcomes in mCRC with an IPT. The occurrence of bevacizumab-related adverse events did not significantly impact survival outcomes.
BACKGROUND: Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood. METHODS: Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT. Progression-free survival (PFS), overall survival (OS) and safety endpoints were analyzed. RESULTS: Of 1204 mCRC patients, 826 (69%) were eligible for inclusion. Bevacizumab use was similar in both arms (IPT (64%) versus RPT (70%)); compared with chemotherapy alone, bevacizumab use was associated with significantly longer PFS (IPT: 8.5 months vs 4.7 months, P = 0.017; RPT: 10.8 months vs 5.8 months, P < 0.001) and OS (IPT: 20 months vs 14.8 months, P = 0.005; RPT: 24.4 months vs 17.3 months, P = 0.004)).1 Bevacizumab use in an IPT was associated with more GI perforations (4.5% vs 1.8%, P = 0.210) but less frequent bleeding (1.5% vs 5.3%, P = 0.050) and thrombosis (1.5% vs 2.7%, P = 0.470), versus chemotherapy alone. Median survival was equivalent between patients that did or did not experience bevacizumab-related adverse events - 20.0 months versus 19.9 months, hazard ratio = 0.98, P = 0.623.1 CONCLUSIONS: The addition of bevacizumab significantly improved survival outcomes in mCRC with an IPT. The occurrence of bevacizumab-related adverse events did not significantly impact survival outcomes.