Globally, the incidence of liver cancer is higher in men than in women, and higher in developing countries than in developed countries, with 50% of liver cancer cases occurring in China.
In 2014, there were 365,000 new cases of liver cancer in China, accounting for 9.59% of all malignant tumor cases and ranking fourth; the number of deaths was as high as 319,000, accounting for 13.88% of all malignant tumor cases and ranking second, just after lung cancer.
Why does liver cancer have a high mortality rate?
Why does liver cancer have a high mortality rate?
Why does liver cancer rank fourth in incidence, but second in mortality in vain?
This is not only related to the rapid progression of the tumor, but also to the limited treatment options. Surgery, interventional and radiotherapy are important tools for long-term survival of patients with early-stage liver cancer, but the postoperative 5-year recurrence and metastasis rate is as high as 40% to 70%.
After recurrent metastasis progresses to advanced liver cancer, the effect of pharmacotherapy is very limited, liver cancer cells themselves have low sensitivity to chemotherapy drugs, and it has been controversial whether systemic chemotherapy can benefit patients.
In the current era of rapid development of targeted therapies, first-line targeted agents for advanced hepatocellular carcinoma were not available until 2007 with the introduction of sorafenib (trade name Doxorubicin/Nexavar).
So what happens when sorafenib becomes resistant and then progresses again? This dilemma has plagued us for a decade, and no established or approved second-line regimen has emerged.
Until April 2017, patients with advanced liver cancer had new hope when the US Food and Drug Administration approved regorafenib for second-line treatment of advanced liver cancer, making it the first targeted drug approved for liver cancer in a decade.
What is the mechanism of action of regorafenib?
Regorafenib (BAYVANGO/Stivarga) is an oral multikinase inhibitor that inhibits the RAF, KIT, RET, PDGFR, VEGFR1, and TIE2 signaling pathways to interfere with tumorigenesis, tumor angiogenesis, and maintenance of the tumor microenvironment, killing tumor cells in multiple ways.
The signaling pathways are deep and complex, and simply put, regorafenib can inhibit tumor cells from multiple angles in a comprehensive manner, with multiple targets being an advantage, but also losing its high specificity.
The drug was previously approved for advanced colorectal cancer and gastrointestinal mesenchymal tumors that have failed with other treatments. So, how well does it work when applied to liver cancer?
How does regorafenib work for liver cancer?
On December 5, 2016, the prestigious medical journal The Lancet published the results of the RESORCE study.
This study included 573 patients with liver cancer, all of whom had advanced disease progression after sorafenib treatment, and randomly assigned patients to the regorafenib and placebo groups, all of whom received treatment until disease progression or intolerable adverse effects.
Results showed that median overall survival was 2.8 months longer in the regorafenib and placebo groups at 10.6 months and 7.8 months, respectively; median progression-free survival was nearly two times longer at 3.1 months and 1.5 months, respectively; and the risk of disease progression was reduced by 54% and the risk of death by 37%.
While all patients on regorafenib experienced adverse reactions, the safety profile was manageable, with the most common Grade 3 or higher adverse reactions being hypertension, hand-foot syndrome, fatigue, and diarrhea.
The safety and efficacy of regorafenib was demonstrated by its ability to significantly improve the overall survival of advanced hepatocellular carcinoma that progressed after treatment with sorafenib.
However, there are limitations to the study; all patients enrolled tolerated sorafenib and progressed on its treatment. If patients are unable to tolerate sorafenib in first-line therapy, can they go directly to regorafenib and be able to tolerate it? This is a direction for further research in the future.
Approved indications for regorafenib in China
In March 2017, the China Food and Drug Administration approved the marketing of regorafenib for the treatment of advanced colorectal cancer and gastrointestinal mesenchymal tumors; in December of the same year, it approved an expanded indication for second-line treatment of advanced hepatocellular carcinoma.
As a malignancy with high incidence and mortality in China, it is significant that liver cancer patients can easily and quickly purchase second-line targeted drugs in China, bringing hope to Chinese liver cancer patients.