Durvalumab: China's First Approved PD-L1 Inhibitor Set to Fill Bladder Cancer Immunotherapy Gap

Shanghai, December 30, 2019 /PRNewswire/ -- Recently, AstraZeneca China announced that the National Medical Products Administration (NMPA) of China has officially approved durvalumab injection (Durvalumab, brand name: Imfinzi), a PD-L1 immune checkpoint inhibitor, for the treatment of unresectable stage III non-small cell lung cancer (NSCLC), drawing significant attention in the oncology community.

Cancer immunotherapy has provided patients with unprecedented treatment opportunities. The PACIFIC study has sparked a “Pacific Storm,” delivering significant clinical benefits to patients with stage III non-small cell lung cancer (NSCLC). In addition to its indication in lung cancer, durvalumab injection has been approved in 11 countries and regions worldwide, including the United States, for the treatment of previously treated advanced bladder cancer, addressing an urgent unmet medical need in this field. It is believed that in the near future, Chinese patients with bladder cancer will also benefit from this novel therapy, achieving prolonged overall survival and improved quality of life.

NearBladder Cancer Treatment Has Progressed Slowly Over the Past 30 Years, Urgently Needing Innovative Therapies

The incidence of bladder cancer in China shows a gradual increasing trend. The age-specific incidence rate remains low before the age of 45 and begins to rise gradually thereafter. The age-specific mortality rate from bladder cancer is low before the age of 60 and increases steadily after that. Both incidence and mortality rates rise with advancing age. Approximately 30%–50% of bladder cancer cases are attributable to smoking, and about 20% are caused by occupational exposures, including those in the textile, dye manufacturing, and rubber chemical industries. Therefore, smokers and individuals with long-term exposure to industrial chemicals are considered high-risk populations for bladder cancer.^[1]。

Over the past three decades, progress in the treatment of advanced bladder cancer has been relatively slow. In early-stage bladder cancer, surgical intervention remains the primary treatment modality, supplemented by intravesical chemotherapy and immunotherapy; standardized treatment protocols can reduce recurrence rates. Nevertheless, approximately 50% of patients experience local recurrence and metastasis within two years post-surgery, and once recurrence or metastasis occurs, the majority of these patients die within two years.^[2]For patients with advanced bladder cancer, traditional treatment primarily consists of chemotherapy; however, its efficacy is limited and it is associated with significant side effects. Patients often experience symptoms such as vomiting, nausea, and loss of appetite, accompanied by a decline in immune function. Consequently, many patients report feeling physically worse during the period following chemotherapy than they did before treatment. Both patients and physicians anticipate that innovative therapeutic approaches will not only extend survival but also improve quality of life.

Tumor Immunotherapy: A “Qualitative Breakthrough” Milestone in Bladder Cancer Treatment

The essence of cancer immunotherapy lies in employing various strategies to evoke and enhance the immune system’s ability to kill tumor cells. PD-L1, or programmed death-ligand 1, is a ligand for PD-1, which serves as a “switch” regulating the proliferation of T cells that play an immune function in the human body. PD-L1 is upregulated in a variety of tumor cells; when it binds to PD-1 on T cells, it inhibits T-cell proliferation and activation, rendering T cells inactive and ultimately enabling tumors to evade immune surveillance and destruction. PD-L1 inhibitors block the expression of PD-L1 on tumor cells, thereby “awakening” T cells and restoring their ability to pursue and eliminate tumor cells within the body.

The emergence of tumor immunotherapy, represented by PD-L1/PD-1 inhibitors, has brought new hope to patients with bladder cancer. In clinical trials of the PD-L1 monoclonal antibody drug durvalumab injection, the median overall survival of patients reached 18.2 months, which is more than twice that of traditional chemotherapy (7.4 months).^[3]。

More fortunately, bladder cancer possesses "inherent advantages" that make it suitable for tumor immunotherapy. The efficacy of tumor immunotherapy is correlated with the level of tumor mutation burden (TMB) in the human body. A higher TMB, indicating a greater density of genetic mutations in the tumor, results in more pronounced differences between tumor cells and normal cells, making the tumor cells easier targets for immune attack and thus enhancing the therapeutic effect of immunotherapy. Compared to other cancers, bladder cancer exhibits a high frequency of genetic mutations and a predisposition to activating mutations, leading to a relatively high TMB. Therefore, theoretically, tumor immunotherapy yields relatively favorable outcomes in bladder cancer.

References:

^[1]2014 Edition of Chinese Guidelines for the Diagnosis and Treatment of Bladder Cancer

^[2]Xiao Juxiang, Wei Xiaohui, Hou Yinyin, et al. Chemotherapy is an important means for the treatment of advanced bladder cancer [J]. Journal of Modern Urology, 2011(03):12-16.

^[3]Bladder Cancer Study 1108