Sorafenib after TACE in hepatocellular carcinoma

I just got back from the Gastrointestinal Cancer Symposium (which many informally call ASCO GI) in Orlando, Florida this week. Not too many "big splash" practice-changing results were presented this year. A few results did catch my attention though, including the negative study from Dr. Okita and colleagues out of Asia involving the use of sorafenib or placebo after transarterial chemoembolism (TACE) for hepatocellular carcinoma. (HemOnc Today has a nice short summary of the oral presentation here).

This was for Childs Pugh Class A patients with a large burden of cancer (at least 10 lesions, or lesions at least 7 cm in size) who had had at least a partial response to TACE prior to enrollment. To the investigators credit, more than 450 patients were enrolled (all from Japan and Korea). Additionally, the majority of patients had hepatitis B or hepatitis C as their underlying risk for hepatoma. Although sorafenib did not extend progression free survival, the treatment was only for a few months after TACE (with a median of 17 weeks on sorafenib and 20 weeks on placebo), and the average sorafenib dose was roughly 200 mg twice a day, which is not the protocol specified 400 mg twice a day, suggesting a lot of adverse events requiring dose modification.

These important exceptions tell me that it may not be that sorafenib is totally ineffective, but that after TACE patients with a high tumor burden may not be able to tolerate much of the drug. The subgroup analysis was interesting as well — Korean patients did substantially better on sorafenib than placebo, unlike the Japanese patients. The reason for this is not clear to me — some single nucleotide polymophism or other gene present only in one population that affects tolerabiliity, metabolism or effectiveness of sorafenib?

Also interestingly, there was a substantial difference between the investigators' assessment of response and the central review, with their being a benefit for sorafenib over placebo seen in the investigator assessments only, which reinforce for me the importance of blinding and central review to eliminate possible biases.