Results-and-Implications-of-SIRFLOX-Part-2.aspx

http://healthcare-executive-insight...sults-and-Implications-of-SIRFLOX-Part-2.aspx

Going back to the SIRFLOX data...
I don't know how widely this publication is read. He is suggesting a move up to post 1st line, and prior to 2nd line chemo. All good stuff.

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This is the second installment of a two-part piece focused on the results of the SIRFLOX study that were presented at ASCO in May. The study, which examined whether the combination of Selective Internal Radiation Therapy (SIRT) with chemotherapy is more effective than chemotherapy alone, had a primary endpoint of overall progression-free survival (PFS). A key secondary endpoint was the "hepatic progression-free survival, and additional secondary endpoints of the SIRFLOX study included tumor response rate, tumor recurrence rate, quality of life, safety and tolerability and the number of previously unresectable patients converted to resectability following treatment. There are many challenges in treating metastatic colorectal cancer (mCRC), and this study aims to provide a new treatment option for patients with unresectable mCRC. You can read background on the study and the treatment using SIR-Spheres Y-90 resin microspheres in part one of this article.
Review of Data Outcome
Analysis of the primary endpoint showed no difference between the two arms; this was not unexpected given SIRT only impacts disease within the liver. While this is important information for physicians to understand, a significant takeaway from SIRFLOX is that patients treated with SIR-Spheres Y-90 resin microspheres in combination with a FOLFOX based regimen (+ bevacizumab), experienced a highly significant improvement in PFS in the liver. In patients who received only a FOLFOX based regimen (+ bevacizumab), tumors in the liver progressed with a median of 12.6 months while those who were also treated with SIR-Spheres Y-90 resin microspheres progressed with a median of 20.5 months, a difference of 7.9 months, and a corresponding 31% lower risk of progression in their liver metastases (Hazard Ratio: 0.69; p=0.002). There was also a statistically significant improvement in hepatic response rate and 6%of patients in the SIRT arm achieved a complete response. Equally encouraging in this patient population is the very minimal and manageable side effects and complications, which compared favorably with those of standard chemotherapy alone. This finding demonstrates for the first time that early integration of SIRT into the treatment strategy for mCRC is safe and well-tolerated.
Implications for Treatment Moving Forward
The SIRFLOX study is truly a landmark study, as this is the largest study of its kind to assess the safety and efficacy of the integration of a percutaneous intervention with standard of care chemotherapy for the management of mCRC. Although SIRFLOX failed to confirm its primary endpoint, the rich data set supports many of the secondary endpoints, and the conclusions we can draw from this study will go a long way in guiding the appropriate use and integration of SIRT into the mainstream management of mCRC.

SEE ALSO: Results and Implications of SIRFLOX, Part 1
As it is too soon to know if there is an Overall Survival (OS) advantage in the first-line setting, it may be too soon to begin the routine integration of SIRT into first-line therapy. However, this robust data set should drive a change in how SIRT is integrated. First, the safety data eases concerns about limiting treatment options following SIRT treatment. That, coupled with the remarkable improvement in liver PFS, suggests that an excellent place to integrate SIRT into mCRC therapy may be immediately following first-line therapy, but before patients begin to progress and enter into second-line chemotherapy or during first-line therapy, as consolidation. One clear advantage of this approach is that most patients do respond to first-line chemotherapy, and reserving SIRT until the success of first-line chemotherapy has been demonstrated, may allow identification of better candidates to proceed for SIRT. Other groups that may potentially benefit from the early addition of SIRT are older patients or patients who otherwise cannot tolerate standard of care chemotherapy or patients whose biological status may limit further lines of systemic therapy, i.e. patients with BRAF or KRAS mutations. The integration of SIRT into these patient populations should significantly improve the effectiveness of traditional chemotherapy and may very well recruit extra patients into the realm of surgical resectability. Either of these outcomes have the potential to extend survival or at the very least improve quality of life for these patients.
Conclusion
The early results from the SIRFLOX study are quite encouraging, and will help guide our utilization of SIRT for the management of mCRC. The strongest conclusions from this study are that early SIRT integration is safe, well tolerated, and dramatically prolongs the time to disease progression within the liver. These conclusions strongly suggest that moving routine integration of SIRT from late in the disease course up to near first-line therapy will significantly extend the time until there is disease progression in the liver, the organ of greatest importance to protect, improve quality of life, possibly prolong survival and may increase the surgical resection rate.
SIRFLOX is the first of a group of three studies assessing the effectiveness of adding SIR-Spheres Y-90 resin microspheres to first-line chemotherapy for the treatment of mCRC. The other studies are FOXFIRE, a UK clinical trial that completed enrollment in November 2014, and FOXFIRE Global, an international study that completed enrollment in January 2015. The results of the three studies, which together enrolled more than 1,100 mCRC patients, will be combined in a pre-planned assessment of the overall survival benefit of adding SIR-Spheres Y-90 resin microspheres to first-line chemotherapy for mCRC. We look forward to evaluating the combined results, which are expected in 2017.
Fred Moeslein, MD, PhD is an assistant professor for Diagnostic Radiology and Nuclear Medicine and Radiation Oncology and the director of Vascular Interventional Radiology at the University of Maryland School of Medicine, Baltimore, Maryland, U.S.