Quality of life in patients with liver metastases from colorectal cancer treated with first-line selective internal radiotherapy (SIRT): Results from the FOXFIRE prospective randomized studies

Background: Quality of life (QoL) in patients with colorectal cancer and liver metastases treated with selective internal radiotherapy (SIRT) using Yttrium-90 resin microspheres combined with FOLFOX (standard chemotherapy) has not been compared to FOLFOX alone. We report QoL results from a prospectively pooled analysis of 3 multicentre randomized trials: FOXFIRE, FOXFIRE-Global and SIRFLOX. Methods: Patients were randomized to FOLFOX or FOLFOX+SIRT in 14 countries. Second-line therapy was permitted upon disease progression. EORTC QLQ-C30 and EuroQoL EQ-5D (3 level) questionnaires were given to all patients at baseline, 2-3, 6 and 12 months from starting treatment and yearly thereafter, and at disease progression. We compared QoL scores between arms at each timepoint, calculating mean differences adjusted for baseline scores, using a 5% significance level. No missing data imputation was performed. Results: 1103 patients were randomised overall. Questionnaire response rates ranged from 92% (1010/1103) at baseline to 33% (163/493) at 24 months. Patients randomised to SIRT showed significantly (p < 0.05) worse scores on 3 of 6 QLQ-C30 functioning scales and 3 of 9 symptom scales (fatigue, nausea and vomiting, appetite loss) at 4-8 weeks after treatment (2-3 months from baseline). SIRT patients had significantly better functioning scores on 3 of 6 scales at disease progression, and significantly less dyspnoea or constipation. Almost no other QLQ-C30 scales showed significant differences at 6, 12 or 24 months. The EQ-5D showed a statistically significant decrement of 0.02 in patients in the SIRT group 2-3 months from baseline, but no differences at other timepoints. Conclusions: This analysis has shown that QoL is slightly impaired in functioning and symptom domains 4-8 weeks after treatment with SIRT+FOLFOX compared with FOLFOX alone, but slightly better when measured at disease progression. These differences were consistent between the QLQ-C30 and EQ-5D instruments. The differences detected were not large enough to be considered clinically significant. Clinical trial identification: FOXFIRE ISRCTN83867919; SIRFLOX NCT00724503; FOXFIRE-Global NCT01721954 Legal entity responsible for the study: University of Oxford Funding: Bobby Moore Fund of Cancer Research UK; Sirtex Medical Ltd Disclosure: I. Chau: Advisory Board: Sanofi Oncology, Eli Lilly, Bristol-Myers Squibb, MSD, Bayer, Roche, Five Prime Therapeutics. Research funding: Janssen-Cilag, Sanofi Oncology, Merck Serono, Novartis. Honorarium: Taiho, Pfizer, Amgen, Eli Lilly, Gilead Science. S. Love: Grants from: Cancer Research UK, Sirtex Medical and non-financial support from Sirtex Medical. J. Moschandreas: Grants from Cancer Research UK, Sirtex Medical and non-financial support from Sirtex Medical. P. Virdee: Grants from Cancer Research UK, Sirtex Medical and non-financial support from Sirtex Medical. P. Tait: Medical advisor and medical proctor for Sirtex medical. H. Wasan: Grants, personal fees, non-financial support and other uncompensated work from Sirtex Medical. G. Van Hazel: Compensation for participation in advisory committees from Sirtex. P. Gibbs: Personal fees from Sirtex. R. Sharma: Research funding, honoraria and consultancy fees from Sirtex Medical. All other authors have declared no conflicts of interest.