New data was presented by Prof. Dr. Volker Heinemann in an oral abstract session at the European Society of Medical Oncology’s 18th World Congress on Gastrointestinal Cancer. The data suggest that patients with liver-dominant mCRC, treated first-line with the combination of mFOLFOX6 and SIR-Spheres Y-90 resin microspheres experienced a profound response to treatment in the liver than those who received chemotherapy alone. This study was recently published by SIRFLOX.
According to Depth of Response (DpR) analysis, a relatively new methodology that has been shown to correlate with overall survival and post-progression survival in earlier mCRC studies, there was a significantly greater Depth of Response (75.0% vs. 67.8% mean reduction in liver tumour burden; p=0.039) in patients who received SIR-Spheres Y-90 resin microspheres combined with chemotherapy. Patients had a statistically significant, two-month longer time to DpR or maximal tumour shrinkage (median 266 vs. 206 days; p<0.001), compared to those who received chemotherapy alone.
The analysis revealed that the treatment effect following SIR-Spheres Y-90 resin microspheres was most evident in the patients who entered the study with a greater baseline liver tumour burden (>12% of the liver having been replaced by tumour, a statistical cut-point that was pre-determined in order to identify potential predictors of DpR).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) and over three-month longer time to DpR (median 298 vs. 196 days; p<0.001) compared to those treated with chemotherapy alone. SIR-Spheres Y-90 resin microspheres was associated with a doubling of median Progression-Free Survival (PFS) in the liver by competing risk analysis (27.2 vs. 13.1 months; p=0.003) in these patients.
Conversely, patients who had a smaller liver tumour burden (≤12%) on study entry were more than six times more 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).
The DpR concept and methodology were developed by Prof. Heinemann and his colleagues in Munich, in collaboration with other experts in treating colorectal cancer. In the SIRFLOX DpR analysis, a novel volumetric model was used to estimate each patient’s spherical liver tumour volume, based on the length of up to five target liver tumours, which were selected during a central independent blinded imaging review of the patients’ baseline and subsequent radiographic images. DpR was then measured by tracking tumour shrinkage until it reached its lowest point, or nadir. In previous DpR analyses of the FIRE-3 study with the biologic agent cetuximab, Prof. Heinemann observed a statistically significant correlation between DpR and overall survival. This observation has also been supported by an evaluation of the TRIBE study.
The predictive value of this approach may be corroborated when overall survival data on the combined SIRFLOX, FOXFIRE and FOXFIRE Global studies of the association of mFOLFOX6 and SIR-Spheres Y-90 resin microspheres in the first-line treatment of colorectal cancer liver metastases become available in 2017.