SARAH Trial - a recap

Had to take my mind away from the budget!

04 March 2015  - data expected late 2016. I assume this is between Sep and Dec?

http://www.sirtex.com/media/39766/20150304-english.pdf
'Sorafenib was established as the standard treatment for patients with advanced HCC following the results of the pivotal SHARP randomized controlled trial, which demonstrated an increased median overall survival from 8 to 11 months compared to placebo.3 However, 80% of patients receiving sorafenib also experienced treatment-related adverse events.'

From the referenced paper
http://www.ncbi.nlm.nih.gov/pubmed/18650514

RESULTS:​

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At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group.​

'Interest in a randomized controlled study of SIRT using Y-90 resin microspheres in this patient population was based on a substantial number of open-label single-group studies as well as a large multi-centre European study on the long-term outcomes related to survival and safety of SIR-Spheres Y-90 resin microspheres in patients with inoperable HCC.4 In 13 open-label singlegroup studies with a total of 400 patients with advanced HCC, the combined estimation of the median overall survival after radioembolization with Y-90 microspheres was 15 months, with a range of 7–27 months. '

From the referenced paper
http://www.ncbi.nlm.nih.gov/pubmed/21618574

The median overall survival was 12.8 months (95% confidence interval, 10.9-15.7), which varied significantly by disease stage (BCLC A, 24.4 months [95% CI, 18.6-38.1 months]; BCLC B, 16.9 months [95% CI, 12.8-22.8 months]; BCLC C, 10.0 months [95% CI, 7.7-10.9 months]). Consistent with this finding , survival varied significantly by ECOG status, hepatic function (Child-Pugh class, ascites, and baseline total bilirubin), tumor burden (number of nodules, alpha-fetoprotein), and presence of extrahepatic disease. When considered within the framework of BCLC staging, variables reflecting tumor burden and liver function provided additional prognostic information. The most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden (nodules >5), international normalized ratio >1.2, and extrahepatic disease. Common adverse events were: fatigue, nausea/vomiting, and abdominal pain. Grade 3 or higher increases in bilirubin were reported in 5.8% of patients. All-cause mortality was 0.6% and 6.8% at 30 and 90 days, respectively.​

CONCLUSION:​

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This analysis provides robust evidence of the survival achieved with radioembolization, including those with advanced disease and few treatment options.​

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Times move on and these data sets are from 2008, and 2011 so the OS may have improved in one or both cases.​

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On a simple level it would suggest that SIRT gives an additional two months. Does not sound a lot, but in % terms it is ~20%. Also consider that many pts do not tolerate Sorafenib too well.​

'However, 80% of patients receiving sorafenib also experienced treatment-related adverse events.'​

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Roll on Sep to Dec.​

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