Liver cancer has become one of the major diseases threatening global human health. The difficulty in the prevention and treatment of liver cancer is that even if it is diagnosed and treated in time, the recurrence rate is still high. In the middle and late stage of liver cancer patients, the situation is even less optimistic. If the cancer spreads to the surrounding lymph nodes, the patient's 5-year survival rate is only 11%. When the cancer spreads to other organs, the 5-year survival rate is only 3%.
Recently, Nature's journal Nature Reviews Drug Discovery summarizes several effective liver cancer therapies around the world.
1. Existing common therapies
From the perspective of mechanism of action, current liver cancer system therapies can be divided into two categories, one is "multi-kinase inhibitor" (MKI), and the other is immunotherapy.
Currently, the US FDA has approved three MKIs. The first is the sorafenib brought by Bayer, approved in 2007, is the first first-line treatment for advanced liver cancer. It is superior to placebo in terms of overall survival gain. But its objective response rate (ORR) is low, only 2%. The second MKI was also brought by Bayer – in April 2017, the US FDA approved the sale of regorafenib for patients who continued to progress after treatment with sorafenib. The third paragraph is the combination of Eisai and Merck (MSD), lervatinib, which is non-inferior to the overall median survival of sorafenib. This is the first systemic therapy approved by the FDA over the past decade for first-line treatment.
In contrast, immunotherapy that can be used to treat liver cancer is not that much. Currently, only Opdivo (nivolumab) has been approved for use in patients who have received sorafenib. Another heavy-weight immunotherapy, Keytruda (pembrolizumab), was granted priority in the treatment of liver cancer in July this year and is expected to be approved in early November.
2. Research therapy
Angiogenesis inhibitors and immunological checkpoint inhibitors are the mainstream of research therapy.
Cabozantinib is an oral MKI that significantly prolonged overall survival and reached the primary clinical endpoint in treated advanced liver cancer patients compared with placebo. This is followed by ramucirumab, a monoclonal antibody that inhibits angiogenesis and targets VEGFR2. In a phase 3 clinical trial, it also prolongs the overall survival of treated patients. However, it is only suitable for patients with high levels of alpha-fetoprotein (AFP) expression. Among those patients whose expression levels are not high, its therapeutic effect is limited.
In the research pipeline, immunotherapy also plays an important role. In addition to Keytruda, which is expected to be approved this month, the pipeline also includes the tislelizumab brought by Baekje Shenzhou and Xinji, and the spartalizumab brought by Novartis. The target of both is PD-1, the former has entered the phase 3 clinical stage, and the latter has also entered the phase 2 clinical research and development. In addition, the PD-L1 inhibitor Tecentriq (atezolizumab), and Imfinzi (durvalumab) and tremelimumab (CTLA-4 inhibitor) are also in clinical development, and Tecentriq has also received a breakthrough therapy approval from the US FDA.
According to the analysis of the journal, according to market share, the drugs that inhibit angiogenesis currently dominate, but immunotherapy will be the first major treatment for liver cancer within 5 years. We expect more new drugs to come out and bring new treatments to patients with liver cancer worldwide.
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