2017 ASCO Annual Meeting!
Session: Gastrointestinal (Colorectal) Cancer
Type: Oral Abstract Session
Time: Monday June 5, 3:00 PM to 6:00 PM
Location: Hall D2
Overall survival analysis of the FOXFIRE prospective randomized studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastases from colorectal cancer.
Gastrointestinal (Colorectal) Cancer
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 3507)
Author(s): Ricky A. Sharma, Harpreet Singh Wasan, Guy A. Van Hazel, Volker Heinemann, Navesh K. Sharma, Julien Taieb, Jens Ricke, Jamie Mills, Nicholas Paul Tait, Philip Boardman, Marc Peeters, Michael P. N. Findlay, Pradeep Singh Virdee, Joanna Moschandreas, Val Gebski, Sharon Love, Alastair Gray, Peter Gibbs; Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom; Hammersmith Hospital, Imperial College London, London, United Kingdom; Sir Charles Gairdner Hospital, Perth, Australia; Comprehensive Cancer Center, Ludwig-Maximilian-University of Munich, Munich, Germany; Penn State Milton S. Hershey Medical Center, Hershey, PA; Hopital Européen Georges Pompidou, Paris, France; University Clinic Magdeburg, Magdeburg, Germany; Oncology Department - City Campus, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom; Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, United Kingdom; Antwerp University Hospital, Department of Oncology, Edegem, Belgium; University of Auckland, Private Bag 92019, Auckland, New Zealand; Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom; Centre for Statistics in Medicine and Oxford Clinical Trials Research Unit (OCTRU), Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford, United Kingdom; National Health and Medical Research Council Clinical Trials Centre, Sydney, Australia; Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; The Western Hospital, Melbourne, Australia
Background: The FOXFIRE, SIRFLOX and FOXFIRE-Global (FF-SF-FFG) randomized studies evaluated the efficacy of combining first-line chemotherapy for metastatic colorectal cancer (mCRC) with selective internal radiotherapy (SIRT) using yttrium-90 resin microspheres in patients with liver metastases. The studies were designed for prospective, combined analysis of overall survival (OS). Methods: FF-SF-FFG randomized (1:1) chemotherapy-naïve mCRC patients (performance status 0/1) with liver metastases not suitable for curative resection/ablation. Arm A was oxaliplatin-based chemotherapy (mFOLFOX6/ OxMdG) ± investigator-chosen biologically targeted agent. Arm B was the same systemic therapy (oxaliplatin dose modification) + single treatment SIRT with cycle 1/2 of chemotherapy. Primary tumor in situ and/or limited extra-hepatic metastases were permitted. Minimum sample size was 1075 patients (HR 0.8, 80% power, two-sided 5% significance). Secondary outcomes included PFS, liver-specific PFS and response rate. Apart from safety, outcomes were analysed on intention-to-treat population using meta-analytic methods of pooled individual patient data. Results: Between 2006 and 2014, 1103 patients were randomized in 14 countries. Median age was 63 years (range 23-89); median follow-up 43.3 months. There were 844 deaths. There was no difference in OS (HR 1.04; 95% CI 0.90-1.19, p= 0.609) or PFS (HR 0.90, CI 0.79-1.02, p= 0.108) between Arms. Objective response rate (p= 0.001) and liver-specific progression (HR 0.51, CI 0.43-0.62, p< 0.001) were significantly more favorable in Arm B. Patients in Arm B had higher risk of non-liver progression as first event (HR 1.98, CI 1.53-2.58, p< 0.001). Grade 3-5 adverse events were more common in Arm B (74.0%) than A (66.5%), p= 0.009. In health status questionnaires, EQ-5D utility scores were not significantly different between Arms at 6, 12 or 24 months. Conclusion: Despite higher response rates and improved liver-specific PFS, the addition of SIRT to first-line oxaliplatin-fluorouracil chemotherapy for patients with liver-only and liver-dominant mCRC did not improve OS or PFS. Clinical trial information: 83867919.
2. Primary (1°) tumor location as an independent prognostic marker from molecular features for overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB / SWOG 80405 (Alliance).