5 month survival benefit in right sided mCRC

This result made the headline in the Sirtex Ann with good reason.  First 38% is a big slice of the mCRC market.  If the liver only mCRC result had gotten up (probably a similar sized market), then the SP would have been well up today.  I note that right sided colon cancers are biologically different from left sided tumours.  They are much more likely to have BRAF mutations (dismal prognostic group refractory to existing therapies), and other molecular changes such as CIMP and MSI (also worse prognosis in mCRC and resistant to therapies).  It may be that radiation therapy delivered by SIRT can kill these tumour types where existing drugs fail, hence the OS benefit. These tumours are also most likely to spread to liver first before systemic involvement, making a liver targeted therapy more logical.  

Pertinent points highlighted from the Ann:

As indicated, an initial exploratory analysis undertaken of the combined SIRFLOX and FOXFIRE Global studies revealed a 4.9 month improvement in median OS in patients who had their primary colon cancer located on the right-side of the colon and who received SIR-Spheres plus chemotherapy versus chemotherapy alone and a 36% decreased risk of death (HR=0.64, p=0.007). Approximately 24% of patients enrolled in these two studies had a right-sided primary tumour....

The data on the impact of primary tumour location on overall survival will be presented at the 19th European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer (WCGIC) in Barcelona, Spain from 28th June to 1st July.

This right-side primary tumour finding from the study requires further investigation......The incidence of right-sided primary colon cancers averages 38% in mCRC patients, based on clinical studies and population-based analysis.  Colon cancer patients who present with a right-sided primary tumour in their colon are clinically more difficult to treat, being less responsive to standard of care chemotherapies and biologic agents.......analyses also support this observation of a worse prognosis with lower overall survival from right-sided primary tumours.

....National Comprehensive Cancer Network (NCCN) guidelines for first-line treatment of mCRC recently included treatment recommendations based on the location of the primary tumour.

The preliminary nature of this study finding means that Sirtex is unable to confirm whether such data is clinically meaningful and likely to result in any change to clinical practice in first-line mCRC patients with a right-sided primary colon cancer. Sirtex anticipates that following presentation of further data at WCGIC and peer review, the Company will be in a position to assess the commercial implications, if any, from presentation of the data and consultation with experts in the field.

They can't outright claim this means 1st line use mandated just yet.  Peer review is needed and it is up to the medical key opinion leaders to provide that kind of recommendation.  But 5 months gain for some of the worst prognosis group tumours sounds like a major finding.  There were clearly sufficient patient numbers to deliver a highly statistically significant result, even though only about a quarter of study cases were in this group.  Discussion at ASCO and WCGIC will be most interesting.