Recently, the results of the first-line treatment of Roche anti-PD-L1 therapy Tecentriq (common name: atezolizumab) combined with Avastin (common name: bevacizumab) in the first-line treatment of unresectable hepatocellular carcinoma (HCC) phase III IMbrave150 study (NCT03434379) were published in the international The top medical journal "New England Medical Journal" (NEJM). The article title is: Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. The data show that Tecentriq+Avastin combination therapy is significantly better than standard nursing drug sorafenib.
IMbrave150 is an open-label, multi-center, randomized phase III study conducted in patients with unresectable, locally advanced, or metastatic HCC who had not previously received systemic treatment. It investigated the combined treatment regimen of Tecentriq and Avastin relative to standard care medications— -The efficacy and safety of multi-kinase inhibition of sorafenib. In the study, patients were randomly assigned in a 2:1 ratio to receive Tecentriq+Avastin combination therapy (n=336) or sorafenib (n=165) until unacceptable toxic reactions occurred or clinical benefit was lost. The common primary endpoint of the study was the overall survival (OS) and progression-free survival (PFS) determined by an independent evaluation agency based on the solid tumor efficacy evaluation standard version 1.1 (RECIST 1.1).
The results showed that the study reached a common primary endpoint: Compared with the sorafenib group, the OS and PFS of the Tecentriq+Avastin combination treatment group showed statistically and clinically significant improvements.
The specific data are: at the main analysis time point (August 29, 2019), compared with the sorafenib group, the overall survival of the Tecentriq+Avastin combined treatment group was significantly prolonged (median OS: NE vs 13.2 months), The risk of death was reduced by 42% (HR=0.58, 95%CI: 0.42-0.79, p<0.001), and the 12-month survival rate was increased (67.2% vs 54.6%). In addition, compared with the sorafenib group, the progression-free survival of the Tecentriq+Avastin combination group was significantly prolonged (median PFS: 6.8 months vs 4.3 months), and the risk of disease progression or death was reduced by 41% (HR=0.59 , 95%CI: 0.47-0.76, p<0.001).
In this study, the safety of the combination of Tecentriq and Avastin was consistent with the known safety of each drug, and no new safety signals were found. Grade 3 or 4 adverse events occurred in 56.5% in the Tecentriq+Avastin combination group and 55.1% in the sorafenib group; 15.2% of patients in the Tecentriq+Avastin combination group developed grade 3 or 4 hypertension; , Other high-level toxic effects are not common.
Liver cancer is a major cause of death globally, especially in Asia, and hepatocellular carcinoma is the most common type. Based on the above results, IMbrave 150 is the first phase III cancer immunotherapy study showing improvement in OS and PFS in the most common liver cancer treatment. The combination of Tecentriq and Avastin is also the first treatment plan to improve overall survival in unresectable hepatocellular carcinoma patients who have not previously received systemic treatment in more than a decade.
In terms of regulation, the US FDA is currently reviewing the supplementary application of the Tecentriq+Avastin combination program through the real-time oncology review pilot project. Previously, the program has been granted breakthrough drug status by the FDA. In China, the plan was accepted by the China National Drug Administration (NMPA) in January this year.
Roche has developed an extensive development plan for Tecentriq, including a number of ongoing and planned phase III studies involving multiple types of lung cancer, genitourinary cancer, skin cancer, breast cancer, gastrointestinal cancer, gynecological cancer, and head and neck cancer. This includes studies on Tecentriq alone or in combination with other drugs.
Tecentriq belongs to PD-(L)1 tumor immunotherapy, which aims to bind to a protein called PD-L1 expressed on tumor cells and tumor infiltrating immune cells to block its binding to PD-1 and B7.1 receptors interaction. By inhibiting PD-1, Tecentriq can activate T cells, and the drug has the potential to be used as a basic combination therapy for cancer immunotherapy, targeted drugs, and various cancer chemotherapy.
Avastin is an angiogenesis inhibitor that targets vascular endothelial growth factor (VEGF). VEGF plays an important role in the angiogenesis and maintenance of the tumor life cycle. Avastin directly infects the blood supply of tumors by directly binding to VEGF, preventing it from interacting with receptors on vascular cells. The blood supply of the tumor is considered to be the key to the tumor's ability to grow and metastasize in the body.
The combination of Tecentriq and Avastin has a strong scientific basis, and the combination of Tecentriq+Avastin has the potential to strengthen the immune system against tumors. In addition to its established anti-angiogenic effect, Avastin can further enhance Tecentriq's ability to restore the body's anti-cancer immunity by inhibiting VEGF-related immunosuppression, promoting T cell tumor infiltration, and initiating T cell responses to tumor antigens.
In December 2018, the US FDA approved Tecentriq+Avastin+chemotherapy (carboplatin and paclitaxel) as first-line treatment for adult patients with metastatic non-squamous non-small cell lung cancer (NSq NSCLC) without EGFR or ALK genome tumor aberrations. The approval is based on data from Group B patients in the IMpower150 study: In intent-to-treat wild-type (ITT-WT) patients, Tecentriq+Avastin+chemotherapy significantly prolonged patient survival compared with Avastin+chemotherapy (median OS: 19.2 months vs 14.7 months, HR=0.78, p=0.016).