Who is the king of non-small cell lung cancer drugs? 2 big PD-1 antibody appears strongly

Lung cancer is one of the most common malignant tumors in the world, and it is also the first tumor incidence rate and mortality rate in China Non small cell lung cancer accounts for 85% of all lung cancers, including squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinoma Compared with small cell carcinoma, the growth and division of cancer cells are slower, and the spread and metastasis of cancer cells are relatively late About 75% of patients were found in the middle and late stage The molecular targeted drug of lung cancer is the most advanced drug for the treatment of tumor Compared with chemotherapy with great toxic and side effects, the most significant advantage of its treatment is that it can target the specific target on tumor cells, accurately attack tumor without damaging normal cells The main therapeutic targets of drugs for NSCLC are EGFR, VEGFR, V600E, RET, HER2, alkret, CTLA4, alkros1, PD-1, PD-L1, etc At present, the list of targeted drugs approved for marketing in the treatment of lung cancer: there are several drugs in the above table that are the focus of the industry: first, according to the nature and function target of the drugs, the most widely used targeted drugs in the treatment of lung cancer are mainly yiruisha (gefitinib) and trokai (erlotinib) It is a representative tumor epidermal growth factor receptor inhibitor; secondly, it brings a new way for tumor treatment - immunotherapy of PD-1 antibody keytruda and opdivo Iressa is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which can block the signal pathway leading to tumor growth This product is suitable for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) which has received chemotherapy before Gefitinib has been proved to improve the antitumor activity of chemotherapy, radiotherapy and hormone therapy in animal experiments or in vitro studies Current situation in China: there is no such drug approved for marketing in China, only imported from Sweden Up to now, there are 68 applications for registration (calculated by acceptance number, the same below), 27 APIs, 41 tablets; of the declared tablets, 6 are imported, 26 are imitated, 9 are applied for supplement, 28 are approved for clinical application, 6 are approved for supplement, and 2 are approved for import Market status: Iressa's global sales grew rapidly in 2012, with a year-on-year growth of 15.7%, and then sales tended to be stable In May 2015, it entered into the first batch of national drug price negotiation list, with a price drop of 55%, and the global sales in this year decreased by 14.8% year on year In addition, gefitinib's US patent will expire on May 5, 2017 (us-05770599), and its sales volume is expected to continue to decline in the future Tarceva is a tyrosine kinase inhibitor of EGFR / HER1 Erlotinib can effectively inhibit the phosphorylation of EGFR, which is usually expressed on the surface of normal cells and tumor cells In non clinical trial models, inhibition of EFGF phosphorylation can cause cell growth arrest and / or cell death Erlotinib alone is suitable for locally advanced or metastasized non-small cell lung cancer (NSCLC) after failure of at least one chemotherapy regimen in the past Current situation in China: the drug is not approved for marketing in China, but only imported from the UK Up to now, there are 133 applications for registration (calculated by acceptance number, the same below), 30 APIs and 103 tablets; of the declared tablets, 28 are imported, 51 are imitated, 24 are supplementary applications, 64 are approved for clinical application, 14 are approved for supplement, and 6 are approved for import Market status: influenced by the fierce market competition, Tarceva's global sales have been declining in the past five years, from US $1283 million in 2011 to US $1029 million in 2015 It is expected that the later sales will be a little difficult Keytruda immunotherapy is a new method to treat cancer It uses drugs to assist the autoimmune system to fight against cancer It has significant effect and little side effects, and is favored by many doctors and patients Currently, there are two approved anti-PD-1 antibodies for the treatment of non-small cell lung cancer: keysruda of mosadong and opdivo of BMS They can fight against cancer cells by inhibiting the PD-1 receptor and helping to restore the activity of immune T cells around cancer cells Keytruda (pembrolizumab) is a new immunotherapy drug developed by mosadon In September this year, keytruda obtained the 6th breakthrough therapy certification issued by FDA and obtained the priority review qualification In October, FDA approved the drug for the treatment of metastatic non-small cell lung cancer patients with high expression of PD-L1 (> 50%) This is the only anti-PD-1 immunotherapy approved for the first-line treatment of non-small cell lung cancer Compared with conventional chemotherapy, it can improve the survival rate of patients Recently, keytruda was approved Because of the failure of opdivo's key phase III research in the first-line treatment of NSCLC, the market wind changed greatly More doctors tend to choose keytruda in the course of drug use, and said that they are willing to test the PD-L1 expression level of patients before the prescription, clearing the obstacles for keytruda's clinical use Keytruda will be a super heavyweight product for first-line treatment of NSCLC, and its market share in second-line treatment of lung cancer will also increase Market status: since keytruda was approved to be listed in September 2014, the sales volume has soared In this year, the global sales volume was US $52 million, reaching US $457 million in 2015, and the sales volume in the first nine months of 2016 was US $919 million It is expected that sales will continue to rise in the later period and reach about 5 billion US dollars in 2020 Opdivo opdivo (nivolumab) is an intravenous injection developed by BMS In September this year, it was approved by FDA to treat anti-PD-1 human monoclonal antibody for recurrent and metastatic non-small cell lung cancer Because it does not need to detect PD-L1 expression level in advance in the second-line treatment of NSCLC and other reasons, keytruda firmly occupies the tumor immunotherapy drug market At present, opdivo has been approved for the treatment of five categories of tumors: melanoma, metastatic NSCLC in or after platinum based chemotherapy, advanced renal cancer RCC previously treated in China, classic Hodgkin's lymphoma CHL, head and neck squamous cell carcinoma It has also been listed in many countries (excluding China) In 2015, the global sales reached 864 million US dollars This year, the situation is even worse In the first nine months of 2016 alone, the global sales reached 2464 million US dollars, and the trend is on the rise At present, nivolumab has 8 import registration applications in China (based on the acceptance number), of which 3 have been approved for clinical application The details are as follows: the current situation of domestic anti-tumor drugs has always been, China's innovation strength in tumor targeted drugs is slightly weak, mainly relying on imports At present, there are three kinds of domestic drugs: exetane hydrochloride, recombinant human endostatin, and xidaban Exetinib hydrochloride is a selective EGFR tyrosine kinase inhibitor with full independent property rights in China, which is suitable for advanced NSCLC after at least one platinum containing chemotherapy failed Registration of domestic clinical trials the author collated the registration of domestic clinical trials of non-small cell lung cancer through the CDE official website As of November 4, 2016, a total of 114 data were found, including 4 duplicates, so a total of 110 effective trial records The registration number is from ctr20130041 to ctr20160774, and the first publicity date is from October 14, 2013 to October 21, 2016 The 110 effective clinical trial registration records include three drug types: 85 chemical drugs (77%), 15 biological products (14%), 10 traditional Chinese medicine / natural products (9%) The above are some information about NSCLC sorted out by the author If there is any incompleteness or error, please correct it Note: This article is original by the author of yaozhi.com, welcome to reprint, please indicate the source and author when reprint, thank you!