Recently, the world's first CTLA-4 inhibitor Yiwo was officially listed in China. As the first and currently the only CTLA-4 inhibitor approved in China, YIWO and PD-1 inhibitor Odyvo were approved by the State Drug Administration of China for adult patients with non-surgically resectable, initially treated non-epithelial malignant pleural mesothelioma. This is the first and currently approved dual immunotherapy in China, marking the official opening of the era of dual immunotherapy in China. The China Cancer Foundation has launched a patient assistance program to provide pharmaceutical assistance to eligible patients.
Malignant pleural mesothelioma puts "armor" on the lungs
Malignant pleural mesothelioma is a rare, highly aggressive, and fatal malignancy that originates in the pleural mesothelium. Professor Wu Yilong, life director of Guangdong Provincial People's Hospital and honorary director of Guangdong Lung Cancer Research Institute (GLCI), said: "In the human chest cavity, there is a tissue called "mesoderm". Mesothelial cells form a protective membrane, the pleura. The pleural mesothelioma makes this layer of pleura into "armor", tightly covering the outside of the lungs. If the lungs are completely confined, the person cannot breathe. It is reported that about 3,000 cases of malignant pleural mesothelioma are confirmed in China every year, accounting for 1/3 of the new cases in Asia. Its incidence is highly correlated with asbestos exposure, and as a major producer and use of asbestos, the incidence of malignant pleural mesothelioma in China shows an increasing trend.
The early symptoms of malignant pleural mesothelioma are not obvious, and the symptoms are mostly advanced in the course of extensive intrathoracic lesions. Because symptoms are inconspicuous and diagnostic difficulties, most patients are advanced at the time of diagnosis. The prognosis of malignant pleural mesothelioma is generally poor, with median survival of previously untreated advanced or metastatic malignant pleural mesothelioma between 12 and 14 months and a five-year survival rate of about 10%.
Lack of effective treatment is the main reason for the low survival rate in patients with malignant pleural mesothelioma. For resectable patients, surgery is preferred, but only a small proportion of patients have the opportunity to operate. For patients with advanced, unresectable or sarcoma-like malignant pleural mesothelioma, the efficacy of traditional chemotherapy is limited, and the objective response rate is only 4% to 15% at the beginning of the advent of chemotherapy drugs, which is not satisfactory. It was not until 2003 that the combined use of pemetrexed with platinum improved the therapeutic response rate of malignant pleural mesothelioma, but the survival of patients was still not significantly prolonged.
Dual immunotherapy was approved, breaking the 15-year deadlock of no new drugs
For more than 15 years, there have been no new systemic treatments worldwide that are effective in prolonging patient survival. In October 2020, the U.S. Food and Drug Administration (FDA) approved Odivo and Yiwo for the first-line treatment of unresectable adult patients with malignant pleural mesothelioma, and dual immunotherapy became the first approved systemic therapy in the field in more than fifteen years. In June 2021, Odivore and Yiwo were approved by the State Drug Administration of China, which is the first and currently the only approved dual immunotherapy in China.
Dual immunotherapy is a unique combination of two immune checkpoint inhibitors that target two different checkpoints (PD-1 and CTLA-4) to help destroy tumor cells, both of which have potential synergistic mechanisms. PD-1 monoclonal antibody combined with CTLA-4 monoclonal antibody immunotherapy can help the human immune system activate and deploy more activated T cells, thereby recognizing, attacking and destroying cancer cells, helping to achieve a long-term anti-tumor immune response, and ultimately helping anti-cancer achieve the effect of "1+1>2".
Xinhua News Agency/AFP
Unlike traditional treatments, immunotherapy may cause inflammatory symptoms in the corresponding organs, called immune-related adverse reactions, with skin and gastrointestinal symptoms being the most common. So will immune-related toxicity also be "1+1>2"? Professor Wu Yilong said: "After a long period of exploration, we have reduced the dose of medication, for example, the dose of CTLA-4 inhibitors has been reduced to 1 mg per kilogram of body weight, and the side effects have been reduced accordingly; in addition, we have also lengthened the time of medication, from once every three weeks to six weeks, and the side effects are lower." Professor Wu Yilong said: "Through the established adverse event management protocol, the first-line treatment of malignant pleural mesothelioma by Odyssey and Yiwo is safe and controllable, and its safety characteristics are consistent with the safety of this combination treatment in other tumor studies. Compared to chemotherapy, patients have the opportunity to achieve long-term survival with a higher quality of life and fewer side effects. With the advent of the era of dual immunotherapy, we are expected to finally achieve the goal of 'de-chemotherapy'. ”
The results of the three-year follow-up of CheckMate-743 showed that the first-line treatment of irresectable malignant pleural mesothelioma in combination with Edworth for non-resectable malignant pleural mesothelioma was a long-lasting survival benefit for patients, regardless of histological type compared with platinum-containing standard chemotherapy. Compared with chemotherapy, patients with dual immunotherapy had a 27% lower risk of death, and nearly 1 in 4 patients survived more than 3 years after receiving dual immunotherapy.
To date, dual immunotherapy based on Odivore and Yiwo has shown total survival (OS) benefits in six phase III clinical studies of five tumors, including malignant pleural mesothelioma, non-small cell lung cancer, metastatic melanoma, advanced renal cell carcinoma, and esophageal squamous cell carcinoma. Wu Yilong said that he hopes that dual immunotherapy for the treatment of other cancers can also be approved in China one after another, so that more patients can benefit.
Patient assistance programs are launched simultaneously to improve access to innovative medicines
In order to help more patients achieve high-quality long-term survival and improve the accessibility of innovative drugs, when Yiwo was listed, Bristol-Myers Squibb and the China Cancer Foundation added new malignant pleural mesothelioma indications to the original "Odevo Patient Assistance Program". Patients who meet the criteria of the program may voluntarily apply for assistance in the joint treatment of Odivore.
Official website of The China Cancer Foundation.
The application process and project materials for new indications will be announced on the official website of the China Cancer Foundation (http://www.cfchina.org.cn/) and the WeChat public account "China Cancer Foundation Odivore Project". Patients can also call the program hotline at 400-669-0906 for consultation.
Written by: Nandu reporter Zeng Wenqiong
Intern: Xu Ziqing