In recent years, targeted therapies have received increasing attention in oncology treatment. Since the approval of trastuzumab (Trastuzumab, trade name Herceptin) for gastric cancer in 2010, targeted therapy has been a boon for countless gastric cancer patients.
So what are the advantages of targeted therapy, and are there any shortcomings?
What is the benefit of targeted therapy?
Prolonged survival
Prolonged survival
As the first large phase III clinical study of trastuzumab for HER2 (Human Epidermal growth Factor Receptor 2)-positive gastric cancer, the ToGA study demonstrated for the first time that chemotherapy combined with targeted agents significantly prolonged survival in patients with advanced gastric cancer, and that chemotherapy combined with trastuzumab significantly prolonged survival compared with chemotherapy alone. The success of the ToGA study announced a new era of molecularly targeted therapy for gastric cancer. The effectiveness of trastuzumab in HER2-positive advanced gastric cancer has subsequently been validated in clinical practice and in other studies, with some patients’ tumors even being converted to resectable.
Well-tolerated
Targeted therapies are “targeted blasts” that target tumor cells, and normal cells are minimally affected because they do not have a target to work on. Targeted therapies are less toxic and better tolerated than conventional chemotherapy. The combination of trastuzumab and chemotherapy has been shown in several studies to have a better safety profile in the treatment of advanced gastric cancer.
What are the limitations of targeted therapy?
Targeted therapy has some limitations along with the benefits it offers.
Limited scope of application
Targeted therapies are not available for all patients. The essence of targeted therapy is that there is a target to follow. The most clinically relevant and widely used target in gastric cancer treatment is HER2, and only gastric cancers that test positive for HER2 should be considered for targeted anti-HER2 therapy.
Currently, trastuzumab is only approved for first-line treatment of advanced gastric cancer, and more is being explored about its use in second-line therapy, cross-line therapy (i.e., continued use in second-line therapy after disease progression in first-line therapy), postoperative adjuvant therapy, maintenance therapy, and more.
Drug resistance
In some patients, initial treatment with targeted agents is effective, yet the lesions are not well controlled after a period of time on the drug. Although there is no clear definition of what constitutes trastuzumab resistance in gastric cancer, the definition in breast cancer is informative. Patients with breast cancer are considered to be resistant to trastuzumab when their disease progresses within 3 months of first-line treatment with trastuzumab or relapses within 1 year of receiving postoperative adjuvant trastuzumab therapy. In the ToGA study, the combination of trastuzumab increased the remission rate by only 12%, and in addition, most patients who initially achieved remission progressed at about 6.7 months, suggesting that gastric cancer cells may be resistant to trastuzumab.
The causes of drug resistance in patients with gastric cancer and the treatment options after drug resistance remain pressing questions.
Expensive
Targeted drugs are generally more expensive because they are more costly to develop and produce. Thankfully, since 2017, many targeted drugs have been covered by health insurance in China, including trastuzumab, which has improved the cost of targeted therapies to a great extent.
Summary
The worldwide HER2 positivity rate for gastric cancer patients is 7.3%-20.2%, and this figure is 12%-13% in Chinese gastric cancer patients, which means that 1 in 6-7 gastric cancer patients in China are HER2 positive. The development of targeted drugs may benefit more patients.
Targeted therapies are highly effective and less toxic, but they also have limitations. Before using a drug, patients should talk to their doctor to choose the most appropriate treatment option for them. (Contributed by Yanwen Diao, Department of Medical Oncology, The First Hospital of China Medical University)