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Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, remains one of the most highly lethal cancers in the world accounting for approximately 600,000 deaths per year making HCC the third leading cause of cancer-related death.  Although there has been good news about the lower incidence of the disease in Southeast Asia and Sub-Saharan Africa due to vaccination programs against hepatitis B, that has not been the case in the US and Europe where both the incidence and the mortality rates of HCC have doubled in the past several decades and are predicted to continue rising because of the concomitant increase in hepatitis C viral infection and the obesity crisis where 36% of the US population is considered obese.

The management of HCC also remains difficult as less than 20% of the patients are eligible for curative treatment at the time of diagnosis and traditional drug therapy has not been extremely effective at prolonging patient survival.  As a result, HCC constitutes a major healthcare problem in the USA and Europe, thereby highlighting the critical need for the development of new effective treatment options to improve patient outcomes.  Fortunately, after the advent of small molecule tyrosine kinase inhibitors such as sorafenib and regorafenib, new check-point inhibitors haven recently proven their worth in a number of clinical trials leading to approval by the FDA.

But never had the FDA approved a combination of drugs for advanced liver cancer.  It has now been achieved as the FDA recently accelerated approval of a combination treatment for patients with advanced liver cancer who were previously treated with sorafenib. This new immunotherapy option consists of a combination of two check-point inhibitors, namely ipilimumab and nivolumab, both monoclonal antibodies.  Ipilimumab (Yervoy) is already approved and used to treat metastatic, late-stage melanoma whereas nivolumab (Opdivo) is already approved for use as monotherapy for advanced HCC.  The results from this combination of check-point inhibitors, part of the CheckMate-040 clinical trial, were highly significant achieving a markedly improved response rate over that of nivolumab alone.  A cohort of 49 patients were treated with nivolumab 1 mg/kg IV and ipilimumab 3 mg/kg IV every 3 weeks for four doses, followed by nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity. After a minimum follow-up of 28 months, 33% of these patients showed some response by imaging, with 8% showing complete and 24% partial response, while demonstrating an acceptable safety profile.

The findings of this study confirm the hope placed in immunotherapy as these drugs demonstrate their ability to generate significant response rates and prolong patient survival.  Finally some progress for the patients who need it the most.