Sirtex's SIR-Spheres Y-90 Resin Microspheres Analyzed in Patients With Liver Metastases From Right-Sided Primary Colon Cancer


July 5, 2017—Sirtex Medical Inc. announced findings from a post hoc data analysis from the 739-patient SIRFLOX and FOXFIRE Global studies. Prof. Guy van Hazel, MD, presented the data at the European Society of Medical Oncology's 19th World Congress on Gastrointestinal Cancer (WCGC) held June 28 to July 1 in Barcelona, Spain.

According to Sirtex, the data indicate that adding liver-directed selective internal radiation therapy (SIRT) with the company's SIR-Spheres yttrium-90 (Y-90) resin microspheres to standard first-line mFOLFOX6 chemotherapy for liver-only or liver-dominant metastatic colorectal cancer (mCRC) in patients with right-sided primary (RSP) tumors led to a statistically significant and clinically meaningful 4.9-month median overall survival benefit (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.46–0.89; P = .007). This translates to a 36% reduction in the risk of death at any given time compared with patients who underwent chemotherapy alone.

Prof. van Hazel commented in the company's press release, "This striking and essentially unexpected finding may bring new hope to mCRC patients with liver-only or liver-dominant tumors that have spread from the right side of the bowel or colon. These cancers are genetically and structurally different from tumors that start on the left side of the colon. Patients with RSP tumors have a worse prognosis for survival and fewer treatment options. They do not respond well to biological therapies such as cetuximab or panitumumab."

As summarized by Sirtex, the analysis of outcomes by primary tumor location that Prof. van Hazel presented at WCGC 2017 was based on new data from SIRFLOX, a 530-patient study first reported at the American Society of Clinical Oncology (ASCO) 2015 annual meeting, and FOXFIRE Global, a 209-patient study that first reported findings at the 2017 ASCO annual meeting, as well as the findings of FOXFIRE, a 364-patient United Kingdom study. In May 2016, the SIRFLOX data were published by Prof. van Hazel et al in Journal of Clinical Oncology(2016;34:1723–1731).

The data from these three studies were prospectively pooled in the 1,103-patient FOXFIRE combined analysis, which was presented at ASCO in June 2017 by Prof. Ricky Sharma, MD. This analysis showed no difference in the primary endpoint of overall survival from adding SIRT to first-line FOLFOX-based chemotherapy in liver-only or liver-dominant mCRC, independent of the site of the patient's primary CRC tumor. However, Prof. Sharma's ASCO presentation did call attention to the finding of a survival benefit for RSP patients treated with SIRT using SIR-Spheres Y-90 resin microspheres and noted that further data would be provided.

Of the 739 patients enrolled in the SIRFLOX and FOXFIRE Global studies and reported by Prof. van Hazel at WCGC, 179 (24.2%) had an RSP tumor and 540 (73.1%) had a left-sided primary (RSP) tumor; 16 (2.2%) patients had a primary tumor in both sides and the primary tumor location was unknown in four patients (0.5%).

As expected, patients with RSPs were older (mean age, 64.4 vs 61.6 years) and a higher proportion were women (42.5% vs 32%), compared to those with LSPs; however, there were no significant differences between the treatment arms by primary tumor location.

Overall survival was significantly improved by the addition of SIRT with SIR-Spheres Y-90 resin microspheres to first-line mFOLFOX6 chemotherapy (± bevacizumab) in mCRC patients with RSP tumors: median 22.0 vs 17.1 months, with or without SIRT, respectively (HR, 0.64; 95% CI, 0.46–0.89; P = .007). No improvement in survival was seen from the addition of SIRT to first-line mFOLFOX6 chemotherapy for patients with LSP tumors (median, 24.6 vs 26.6 months), with or without SIRT, respectively (HR, 1.12; 95% CI, 0.92–1.36; P = .279).

The Chi-square test of treatment interaction by location for overall survival also proved highly significant (9.49; HR, 0.548l; 95% CI, 0.37–0.8; P = .002;), providing further evidence that the observed benefit of adding SIRT to mFOLFOX6 chemotherapy in RSP mCRC patients was not a chance finding.

Patients with RSP tumors treated with SIRT plus mFOLFOX6 also showed a trend toward improved progression-free survival compared with those who received mFOLFOX6 alone (median, 10.8 vs 8.7 months, respectively; HR, 0.73; 95% CI, 0.53–1.01; P = .053).

There were no significant differences in the incidence of adverse events between patients with RSP tumors and those with LSP tumors. "Although adverse events were more common in the chemotherapy plus SIRT group of the combined analysis, these were generally predictable and manageable," noted Prof. van Hazel.

Prof. van Hazel also observed, "The location of the primary tumor in mCRC is emerging as a major prognostic factor and predictor of response to treatment. Patients with mCRC from right-sided primary tumors clearly have a worse prognosis and an inferior response to treatment compared to patients with left-sided primaries. Our analysis of the impact of primary tumor location on outcomes in the SIRFLOX and FOXFIRE Global studies cohorts shows that the addition of SIR-Spheres Y-90 resin microspheres to first-line FOLFOX-based chemotherapy was associated with a statistically significant and clinically relevant gain in overall survival for patients with a right-sided primary tumor."

"We believe that our data add to the growing literature on the impact of primary tumor location on mCRC outcomes, which has been observed with various treatments and may, if validated, support a side-based approach to patient selection for SIRT in first-line treatment of liver-only or liver-dominant mCRC," concluded Prof. van Hazel in the Sirtex press release.


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