On Sorafenib and the resurrection of other systemic therapies


By J F Geschwind.

Despite the recent approval by the FDA of sorafenib the first systemic therapy for HCC, the outcome for most patients with hepatocellular carcinoma (HCC) remains bleak. Why is this?


Unlike most diseases in medicine, HCC is actually two diseases in one; the cancer itself and also the chromic underlying damage to the liver or cirrhosis.  As a result, treating patients with HCC remains extremely difficult, especially for those (by far the vast majority) who are not transplant candidates. As it is for all other cancers, therapy is always a delicate balance between efficacy and toxicity, but this is especially so in HCC because of the fragile state of the liver. So where are we today, where are we headed and what are some of the controversies associated with HCC?


There has been some real progress since, as mentioned above, there is now an approved and somewhat effective systemic treatment for HCC based on the targeting by sorafenib of specifically up-regulated pathways in HCC. This is a first for systemic therapies after more than 30 years of fruitless attempts through countless clinical trials. There has also been tremendous improvements in loco-regional intra-arterial approaches to HCC after years of stagnation with the advent of drug-eluting microsphere technology which allows greater drug concentration within the tumour and concomitant minimised toxicities than seen with conventional regimens such as chemoembolisation or chemoinfusion, translating into improved efficacy and lower toxicity profile.


The combination of these two therapies, drug-eluting microspheres chemoembolisation and targeted systemic therapy, is therefore extremely appealing. Clinical trials testing this new combination are under way throughout the world, and results should become available next year. Hopefully, the results of these trials will show unequivocally that combining this more potent form of intra-arterial therapy with a targeted systemic agent is the way to go, leading to significant survival benefit.


But the road ahead might not be that simple. Indeed, many pharmaceutical companies and medical oncologists, enamoured by the success of sorafenib have resurrected all sorts of systemic approaches for HCC. Despite unsuccessful attempts in the past 30 years costing patients their lives and the health care system large sums of money, we are again on the cusp of another wave of clinical trials designed to test various systemic therapies, which for the most part had largely been abandoned such as conventional chemotherapy. These trials look to incorporate conventional chemotherapy with newer and more effective targeted agents.

As interventional oncologists, we have been playing a key role – through the years – in the management of patients with HCC. It is time to be vigilant in order to avoid repeating the same mistakes. We owe this not to ourselves as physicians, but of course to our patients who have been waiting desperately for a fighting chance against this highly lethal disease.

J F Geschwind is professor of Radiology, Surgery and Oncology and director, Interventional Radiology Centre, Johns Hopkins University School of Medicine, USA.