Olapari gets FDA approval to treat prostate cancer!

Introduction: prostate cancer BRCA1 / 2 mutations or ATM biomarker subgroup of patients, only PARP inhibitors to improve overall survivalAstraZeneca and Merck announced today, Lynparza (olaparib) has been approved by the FDA for metastatic castration has homologous recombination repair (HRR) gene mutations resistant prostate cancer (mCRPC) patientsThe FDA-approvedis based on the results published in the "New England Journal of Medicine" (newenglandjournalofmedicine) Phase III trial of depthThe main endpoint of the trial is BRCA1 / 2 gene mutation or ATM (HRR gene mutations in a subgroup) Men progression-free survival (rPFS)The results showed that, Lynparza a 66% reduction of the risk of disease progression or death (hazard ratio equivalent to 0.34; p-value <0.0001), and rPFS increased to a median of 7.4 months, and the use Enzha Lu amine or Upbeat Long median was 3.6 monthsresults April 24, 2020, released, or suffering mCRPC ATM mutations and male BRCA1 / 2 in, Lynparza compared to amine or abiraterone Enzha Lu, overall survival (OS ) the key secondary endpoint was significantly improved and clinically meaningfulThe results showed that, Lynparza reduce the risk of death by 31% (corresponding to a hazard ratio of 0.69; p-value = 0.0175), and increase to a median OS of 19.0 months, while the use of amine or abiraterone was Enzha Lu 14.6 monthsCurrently, Lynparza undergoing regulatory review for the treatment of male indications have the HRR gene mutation mCRPC of the European Union and other jurisdictionsprostate cancer Prostate cancer is the second most common cancer in men, it is estimated that prostate cancer patients newly diagnosed worldwide in 2018 1.3 million associated with significant mortalityThe development of prostate cancer is usually caused by male sex hormones (called androgens) drive, including testosteroneWhen the current prostate cancer grow and spread to other body parts, despite the use of androgen deprivation therapy to block the action of male sex hormonesAbout 10-20% of patients with advanced prostate cancer will develop CRPC within five years, of which at least 84% of the patients in that time there will be transfer of CRPC diagnosisMen in CRPC diagnosis no metastasis, 33% likely to metastasize within two yearsAlthough the number of available methods of treatment of mCRPC men has increased, but the 5-year survival rate is still lowHRR gene mutationHRR gene mutations occur in approximately 20-30% of patients mCRPC HRR gene in normal cells can be accurately repair the damaged DNA HRR defects (HRD) interfere with normal cellular DNA repair mechanisms can lead normal cell death This is different in cancer cells, resulting in mutations HRR pathway abnormal cell growth leading to cancer DNA damage can not be repaired properly lead to genomic instability and contribute to the etiology of cancer HRD is a PARP inhibitor (e.g Lynparza) valid target PARP inhibitors block PARP by DNA damage repair mechanism capture DNA single strand breaks in combination, resulting in stalled replication forks, resulting in DNA double strand breaks, leading to cell death Lynparza Lynparza (Austrian Lapa Li) and AstraZeneca Merck jointly developed a "first-in-class" PARP inhibitors, targeted therapies is also a first DNA damage response (DDR) cell / tumor blocking, the therapy the presence of homologous recombination repair defects, such as BRCA1 and / or BRCA2 mutations With Lynparza PARP inhibition, leading to DNA strand breaks and PARP binding, replication arrest bifurcation, folding, DNA double strand breaks, cell death Lynparza series of PARP-dependent tumor is detected, these defects and tumors dependent pathway in the DDR Lynparza currently approved in several countries including the European Union for the maintenance treatment of recurrent ovarian cancer sensitive to platinum In the United States, European Union, Japan, China and several other countries, it is approved as maintenance therapy after first-line platinum-based chemotherapy BRCA mutation of advanced ovarian cancer United States, Japan and some other countries have approved the use of drug therapy germline BRCA mutation, HER2-negative metastatic breast cancer previously treated with chemotherapy; in the EU, including the treatment of locally advanced breast cancer Lynparza is approved for the treatment of metastatic pancreatic cancer BRCA germline mutations in the United States and several other countries For ovarian cancer, breast cancer, pancreatic cancer and prostate cancer regulatory review is ongoing References Bray et al (2018) Global cancer statistics 2018:. GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA: A Cancer Journal for Clinicians, 68 (6), pp .394-424 Cancer.Net (2019) Treatment of metastatic castration-resistant prostate cancer treatment-metastatic-castration-resistant-prostate-cancer [Accessed: November 2019] Kirby, M., 2011 Characterising the castration-resistant prostate cancer population:. a systematic review International Journal of Clinical Practice, 65 ( 11), pp.1180-1192 Mateo, J, et al (2015) DNA-repair defects and olaparib in metastatic prostate cancer New England Journal of Medicine, 373 (18), pp.1697 -. 1708 Li et al (2008) Homologous recombination in DNA repair and DNA damage tolerance Cell Research, 18 (1), pp.99-113 Ledermann et al (2016) Homologous recombination deficiency and ovarian cance r European Journal of Cancer, 60, pp.49-58 Editor: Meng Meng Related tags: U.S , Austria La Pali , AstraZeneca , a prostate cancer, Merck 0 0