First of all, it should be noted that there is no targeted drug that can treat esophageal cancer that has been approved for clinical use, both domestically and internationally.
While there are many potential therapeutic targets for esophageal cancer and the prospects for treatment with targeted drugs are promising, the targets are scattered, making it difficult for scientists to focus their firepower.
At present, most potential targeted drugs for esophageal cancer are still in clinical trials or preclinical studies. There is still a long way to go before they can actually be used on patients.
Right now, only targeting drugs that target the epithelial growth factor receptor (EGFR), such as nitrozumab and gefitinib, have shown some efficacy in some participants in clinical trials.
Potential target agents for esophageal cancer, there are two main categories:
Monoclonal antibodies
Nimotuzumab is a monoclonal targeted drug, the first monoclonal drug for the treatment of malignant tumors in China, under the trade name of “Tyson”, which is mainly used in the combination of radiotherapy for EGFR-positive mid-stage (stage III/IV) nasopharyngeal carcinoma.
In a clinical study of esophageal cancer in China, a response rate of 51.8% was achieved with “nitrozumab in combination with first-line chemotherapy” and a response rate of 52.4% was achieved with “nitrozumab in combination with radiotherapy” in patients who were not suitable for chemotherapy. Patients who were not suitable for chemotherapy could achieve a response rate of 52.4% if they were treated with “nitrozumab combined with radiotherapy. In other words, the two targeted therapies in the study were effective in more than half of the patients. In addition, the disease control rates in both studies were above 90%, which means that 90% of the patients had some degree of remission after treatment.
Small molecule targeted drugs
Small-molecule inhibitors of EGFR are also showing early success in patients with esophageal cancer, mainly with the suffix “tinib.
A phase III clinical study showed that gefitinib was more effective than adenocarcinoma as second-line therapy in patients with squamous esophageal cancer. In particular, patients found to be positive for EGFR expression by genetic testing are better suited for this therapy.
Data from China showed that 90% of patients who were intolerant to platinum-based chemotherapy improved after switching to radiation therapy combined with gefitinib.
Ecotinib, the first original small-molecule targeted agent in China, was also effective in second-line treatment of patients with EGFR-positive esophageal cancer.
These drugs are still in follow-up clinical trials. Meanwhile, some novel anti-EGFR drugs, such as panitumumab and afatinib, are also in the trial phase and are recruiting appropriate patients with esophageal cancer.
Antiangiogenic therapy
Antiangiogenic therapy, a treatment using vascular-targeting drugs, may also be used in the future for esophageal cancer.
Vascular-targeted drugs primarily improve the microenvironment around the tumor and block the production of blood vessels that feed the tumor. If you compare a tumor to an invading army, the microenvironment around the tumor is the “food and grass,” and chemotherapy is a direct attack on the tumor itself, while anti-angiogenic drugs can cut off the “food and grass. The anti-angiogenic drugs can cut off the supply of “food and grass”. The combination of the two, together with the tumor, makes the treatment more effective.
In 2018, the American Society of Clinical Oncology (ASCO) reported on the results of the domestic targeted drug Apatinib a drug that targets endothelial cells. This is a vascular targeting agent against vascular endothelial growth factor receptor 2 (VEGFR-2). In a study of esophageal squamous carcinoma, apatinib alone or in combination with radiotherapy as second-line therapy had response and disease control rates of 34.1% and 77.3%, respectively, with median disease-free progression and survival of 3.87 and 5.93 months, respectively; moreover, adverse effects were manageable.
Another retrospective study found that for esophageal squamous carcinoma, apatinib alone as second-line therapy resulted in a 24.2% response rate and 74.2% disease control; however, 59.7% of patients were associated with some degree of adverse events.
There are several clinical trials that have included apatinib in studies of second-line therapy.
Taken together, these targeted agents are generally effective in treating patients with esophageal cancer, and the outlook is promising, but further screening of the population that could benefit from them is needed.