In recent years, emerging molecularly targeted drugs have been the potential stocks in the anti-cancer circle. They are like “biological missiles” in the body, which can precisely target a cancer-causing site for “advanced tailoring”.
After entering the body, the targeted drugs will target this specific site and kill the tumor cells specifically, and rarely affect the surrounding normal tissues, which makes up for the defect of radiotherapy that “kills a thousand enemies but loses a hundred”.
Especially for advanced hepatocellular carcinoma, which is inoperable and the effect of radiotherapy is not good, targeted drugs have been a hot spot for research, but no new progress has been made.
Today, we’re introducing lenvatinib mesylate (also known as lenvatinib), a “rising star” that just made a major breakthrough in targeted liver cancer therapy in 2018.
Lenvatinib: the “new dark horse” after a decade of trials
Since its approval in the US in 2007, sorafenib has long been the dominant drug in liver cancer treatment, and is currently the only molecularly targeted drug approved for advanced liver cancer in China.
In March 2018, a “dark horse” suddenly emerged in the liver cancer treatment world, with the approval of lenvatinib mesylate (trade name Lenvima) as a first-line treatment for non-surgically resectable hepatocellular carcinoma in Japan, based on a phase III clinical trial published in early 2018. This is the first line of treatment for lenvatinib. This is one of the “first in the world” for lenvatinib.
In August 2018, the U.S. Food and Drug Administration (FDA) approved lenvatinib for the first-line treatment of patients with unresectable hepatocellular carcinoma.
On September 4, 2018, the State Drug Administration (NMPA) of China also approved the marketing of lenvatinib mesylate for the first-line treatment of unresectable hepatocellular carcinoma patients who have not previously received systemic therapy. Patients with advanced hepatocellular carcinoma in China now have a new option.
What is this drug that has been fast-tracked for approval in Japan, the United States, and China?
Lenvatinib breaks the monopoly of sorafenib
The phase III clinical trial, called the REFLECT study, published in the Lancet, is a global multicenter clinical study that evaluated the efficacy and safety of lenvatinib mesylate in the first-line treatment of unresectable hepatocellular carcinoma, and compared it with sorafenib.
The data showed that the median overall survival in the sorafenib group was 12.3 months, compared to 13.6 months in the lenvatinib mesylate group. This indicates that lenvatinib mesylate is no less effective than sorafenib in prolonging survival time.
Also, compared to sorafenib, lenvatinib mesylate delivered superior results in terms of progression-free survival (7.4 months vs. 3.7 months), time to disease progression (8.9 months vs. 3.7 months), and objective remission rate ( 24% vs. 9%).
In other words, patients with advanced hepatocellular carcinoma were able to effectively control disease progression and achieve high-quality survival almost twice as long as sorafenib with this oral drug!
In addition, lenvatinib mesylate can effectively delay the deterioration of symptoms, and the incidence of adverse reactions such as hand-foot syndrome, hair loss and diarrhea is less than that of sorafenib.
In a nutshell: Lenvatinib mesylate is not worse than sorafenib, even better in terms of tumor control and improving the quality of survival! Since then, lenvatinib mesylate has broken the 11-year monopoly of sorafenib in the field of targeted therapy for advanced liver cancer.
How does lenvatinib work
Lenvatinib mesylate is an oral multi-receptor tyrosine kinase (RTK) inhibitor.
“Tyrosine kinase” is like fertilizer for cancer cells and is closely related to their growth. Studies have shown that more than half of all oncogenes and oncogene products are associated with tyrosine kinase activity. “Tyrosine kinase inhibitors are designed to inhibit tumor growth by blocking the molecular mechanisms involved.
Lemvatinib mesylate is also a “multi-faceted” inhibitor, inhibiting the activity of several different targets simultaneously: vascular endothelial growth factor receptor (VEGF), fibroblast growth factor receptor ( VEGF), fibroblast growth factor receptor (FGFR), and other pathway-related regulators associated with changes in tumor angiogenesis, tumor progression, and tumor immunity.
Prior to its use in the treatment of liver cancer, lenvatinib mesylate was approved for the treatment of other cancers. For example, it has been approved in more than 50 countries worldwide for the treatment of refractory thyroid cancer and in the U.S. and EU for patients with advanced renal cell carcinoma who have previously received VEGF-targeted therapy.
Of course, as an anti-cancer drug, lenvatinib mesylate inevitably has many side effects. Among them, there are 28 side effects with an incidence of more than 10%, including hypertension (73%), diarrhea (67%), weakness (67%), arthralgia/myalgia (62%), decreased appetite (54%), weight loss (51%), and nausea (47%).
Despite this, the medical need is far from being met as treatment options for non-surgically resectable hepatocellular carcinoma are very limited and the prognosis is extremely poor. Lenvatinib mesylate is expected to bring new hope to patients with hepatocellular carcinoma.