SUMMARY OF THE SIRFLOX RESULTS

Transcription

1 SUMMARY OF THE SIRFLOX RESULTS The SIRFLOX study results on the combination of SIR-Spheres Y-90 resin microspheres with first-line chemotherapy were published in Journal of Oncology in early There were no significant differences in baseline patient characteristics. A majority of patients had poor prognostic factors at baseline (extra-hepatic metastases, primary tumour in situ, synchronous metastases). 1 The results from this first large-scale, randomised controlled trial of 530 chemotherapy-naive patients with liver-only or liver-dominant metastatic colorectal cancer (mcrc) showed that there was no statistically significant improvement in PFS at any site with the addition of SIR-Spheres Y-90 resin microspheres, a finding that was not unexpected with a liver-directed treatment. However, the risk of first progression in the liver as per competing risk analysis remained significantly lower for patients receiving SIR-Spheres Y-90 resin microspheres. The improvement was 7.9 month with an HR of 0.69 corresponding to a 31% reduction in risk of progression in the liver at any point in time. 1

2 The treatment effect following SIR-Spheres Y-90 resin microspheres were most evident in the patients with a greater baseline liver tumour burden (>12% of the liver having been replaced by tumour, a statistical cut-point that was predetermined in order to identify potential predictors of Depth of Response). In this group of more compromised patients, SIR-Spheres Y-90 resin microspheres were associated with a doubling of median PFS in the liver by competing risk analysis (27.2 vs.13.1 months; p=0.003). 2 The Depth of Response (DpR) concept, a new methodology, aims to relate the degree of observed tumour shrinkage to post-progression survival. DpR is measured by tracking the percentage of tumour shrinkage at its lowest point, or nadir, compared with baseline. 3 DpR has been shown to correlate with overall survival (OS) and post-progression survival in earlier mcrc studies. 4 Adapted from Heinemann V et al. ESMO WCGIC, Ann Oncol 2016; 27 (Suppl 2): Abs. O-014.

3 In SIRFLOX, the addition of SIR-Spheres Y-90 resin microspheres in combination with first line chemotherapy significantly increased hepatic DpR. 2 The treatment effect following SIR-Spheres Y-90 resin microspheres was most evident in patients with a greater baseline liver tumour burden (>12% of the liver having been replaced by tumour, a statistical cut-point that was predetermined in order to identify potential predictors of DpR). This group of more compromised patients, representing over half the patients in SIRFLOX, experienced a statistically significant, 20% greater DpR (77.5% vs. 57.2%; p=0.003) compared to those treated with chemotherapy alone. 2 Additionally, patients who received SIR-Spheres Y-90 resin microspheres demonstrated an increase of over 100 days in Time to Nadir.

4 Objective Response Rate (ORR) in the liver was a secondary endpoint of the SIRFLOX study. SIR-Spheres Y-90 resin microspheres in combination with first line chemotherapy, versus chemotherapy alone, showed a significant increase of 9.9% in ORR in the liver and a three-fold improvement in complete response rate (CR) in the liver. 1 Patients who had a smaller liver tumour burden ( 12%) on study entry were more than six times as likely to experience a complete response or disappearance of all liver tumours following SIR-Spheres Y-90 resin microspheres compared to those who received only chemotherapy (11.3% vs.1.7%; p=0.003). 2 In the SIRFLOX study, the addition of SIR-Spheres Y-90 resin microspheres did not adversely affect the delivery of chemotherapy. Furthermore, the safety profile of the addition of SIR-Spheres Y-90 resin microspheres to the mfolfox6 chemotherapy regimen in SIRFLOX was as anticipated and manageable, with no unexpected toxicities observed.

5 The table below lists selected Grade 3 adverse events from the SIRFLOX study. Denotes statistically significant difference in incidence of adverse event bev*: bevacizumab (bevacizumab allowed at investigator s discretion, per institutional practice) 1. van Hazel GA et al. J Clin Oncol 2016; 34: Heinemann V et al. ESMO WCGIC, Annals of Oncology 2016; 27 (Suppl 2): Abs. O Mansmann UR et al. J Clin Oncol 2013; 31 (Suppl): Abs Heinemann V et al. Eur J Cancer 2015; 51: