Immunotherapy for lung cancer! AstraZeneca imfinzi first-line treatment of extensive small cell lung cancer (SCLC) by the U.S. FDA priority review!

November 30, 2019 / BIOON / -- AstraZeneca recently announced that the U.S Food and Drug Administration (FDA) has accepted and granted SBLA for first-line treatment of patients with extensive small cell lung cancer (es-sclc) with PD-L1 tumor immunotherapy, imfinzi (durvalumab) FDA has designated the first quarter of 2020 as the target date for the prescription drug user fee Act (PDUFA) of SBLA SCLC is an aggressive and fast growing cancer Although initially responding to chemotherapy with platinum, it will recur and progress quickly This SBLA is based on the positive data of phase III Caspian test The results showed that fixed dose of imfinzi combined with SOC chemotherapy with platinum significantly improved the overall survival (OS) compared with standard nursing (SOC) chemotherapy with platinum Based on the results of this study, imfinzi is the first tumor immunotherapy to show birth survival benefits and improve long-term remission in es-sclc patients Caspian is a randomized, open label, multicenter, global phase III study, comparing the efficacy and safety of imfinzi + SOC chemotherapy with platinum (etoposide + cisplatin or carboplatin), imfinzi + tremelimumab + SOC chemotherapy with platinum, and SOC chemotherapy with platinum for es-sclc patients Among them, the combination of imfinzi + tremelimumab + SOC chemotherapy with platinum is a combination chemotherapy scheme with double immunocheckpoint blocking, which is composed of CTLA4 checkpoint inhibitor tremelimumab (an anti-CTLA4 monoclonal antibody), PD-L1 checkpoint inhibitor imfinzi (an anti-PD-L1 monoclonal antibody) and SOC chemotherapy In the study, patients in the experimental group received up to four cycles of SOC chemotherapy, while patients in the control group were allowed up to six cycles of SOC chemotherapy and preventive brain radiotherapy (PCI) The study was conducted in more than 200 clinical centers in 22 countries, including the United States, Europe, South America, Asia and the Middle East The primary end point was overall survival (OS) A planned mid-term analysis conducted by the independent data monitoring committee (IDMC) concluded that the study had reached the primary end point, which showed that the imfinzi + SOC chemotherapy group had a 27% lower risk of death (HR = 0.73, 95% CI: 0.591-0.909, P = 0.0047), significantly longer overall survival (median OS: 13.0 months [11.5, 14.8] vs 10.3 months [9.3], 11.2) and 18 month survival rate increased significantly (33.9% vs 24.7%) In addition, the imfinzi + SOC group showed a significant improvement in progression free survival at 12 months (PFS: 17.5% vs 4.7%), an increase of 10.3% in objective response confirmed at 12 months (ORR: 67.9% vs 57.6%), and an increase in the proportion of patients with sustained response at 12 months (DOR: 22.7% vs 6.3%) In this study, the safety and tolerability of imfinzi + SOC chemotherapy regimen were consistent with previous studies 61.5% of patients in imfinzi + SOC group had grade 3 or grade 4 adverse events, 62.4% in SoC group, and the proportion of patients in two groups who stopped treatment due to adverse events was similar (9.4% vs 9.4%) At present, imfinzi is also being tested in another phase III clinical study, Adriatic, to evaluate the time limit for patients with SCLC to receive imfinzi treatment after concurrent radiotherapy and chemotherapy (CCRT) Jose baselga, executive vice president of oncology research and development of AstraZeneca, previously said: "the results of the phase III CASPIAN study are very encouraging More than one third of the SCLC patients receiving imfinzi + SOC chemotherapy are still alive at the 18 month milestone Given the invasive nature of the disease, this result is significant It is worth noting that these results may lead doctors to choose imfinzi combined with cisplatin or carboplatin chemotherapy backbone therapy We look forward to working closely with regulators to bring imfinzi to SCLC patients around the world as soon as possible " Dr Luis Paz Ares, chief investigator of Caspian research, Department of oncology, University Hospital of oktob, Madrid, Spain, previously said: "patients with SCLC have limited choice of treatment, which is a devastating disease with a 5-year survival rate of less than 6% The strong efficacy data of Caspian study shows that imfinzi combined with 4 cycles chemotherapy has significant survival benefits compared with up to 6 cycles chemotherapy and preventive brain radiation therapy (PCI) programs These data provide evidence and hope for new treatment options for patients with SCLC " Lung cancer is the leading cause of cancer death in men and women, accounting for about one fifth of all cancer deaths Lung cancer can be roughly divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), of which SCLC accounts for about 15% About two-thirds of patients with SCLC are diagnosed with generalized disease, i.e cancer has spread widely to the whole lung or other parts of the body SCLC is an aggressive and rapidly growing cancer Although initially responding to chemotherapy with platinum, it recurred and progressed rapidly The prognosis is very poor Only 6% of SCLC patients survive 5 years after diagnosis Imfinzi is a kind of PD-L1 immunotherapy, targeting to combine with programmed cell death factor ligand 1 (PD-L1), blocking the interaction of PD-L1 with PD-1 and CD80, antagonizing the immune escape strategy of tumor and releasing the inhibition of immune response In terms of lung cancer, up to now, imfinzi has been approved by 54 countries (including the United States, the European Union and Japan) for the treatment of non resectable locally advanced (stage III) NSCLC patients This approval is based on data from the phase III study Pacific study According to the three-year OS data released at the annual meeting of the American Society of Clinical Oncology (ASCO) in early September this year, persistent and sustained OS benefits were observed in patients with unresectable stage III NSCLC who did not progress after concurrent radiotherapy and chemotherapy (CRT): the three-year OS rate of the imfinzi treatment group was 57%, the median OS rate was not yet reached, the three-year OS rate of the placebo group was 43.5%, and the median OS rate was 29.1 months Based on this result, imfinzi became the first immunotherapy to be confirmed to have a 3-year survival benefit in an unresectable stage III NSCLC population At present, AstraZeneca is carrying out a large-scale clinical project to evaluate the treatment of NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, cervical cancer, cholangiocarcinoma and other solid tumors with imfinzi as single drug therapy and combined therapy with tremelimumab and its drugs Source: imfinzi granted FDA priority review for the treatment of patients with extended stage small cell lung cancer