Olaparib ( AZD-2281 , trade name Lynparza ) is an FDA-approved targeted therapy for cancer, developed by scientists at Sheffield University, Pharmacy KuDOS and then by AstraZeneca. This is a PARP inhibitor, inhibiting ADP ribose polymerase (PARP) poly, the enzyme involved in DNA repair. Act against cancer in people with BRCA1 mutations or BRCA2 herediter, which includes some ovarian, breast, and prostate cancers.
In December 2014, olaparib is approved for use as sole agent by EMA and FDA. The FDA approval is for mutated BRCA germline (gBRCAm) advanced ovarian cancer that has received three or more previous chemotherapy lines. In January 2018, olaparib became the first FDA-approved PARP inhibitor for metastatic breast cancer gBRCAm.
Video Olaparib
Action mechanism
Olaparib acts as an enzyme in poly ADP ribose polymerase (PARP) enzyme, and is referred to as a PARP inhibitor. BRCA1/2 mutations may be genetically susceptible to the development of some forms of cancer, and may be resistant to other forms of cancer treatment. However, these cancers sometimes have unique vulnerabilities, as cancer cells have increased dependence on PARP to repair their DNA and allow them to continue to divide. This means that drugs that selectively inhibit PARP may be beneficial if the cancer is susceptible to this treatment.
Maps Olaparib
Clinical studies
Phase I clinical trials show activity in advanced, ovarian and prostate breast cancer that no longer responds to previous therapies, including prostate cancer resistant to the lacerations that have been responded to for several years; activity is seen primarily in ovarian cancer.
In 2009, phase II clinical trials of olaparib started in breast, ovarian and colorectal cancers. Activity was seen in ovarian cancer, with 7 responses in 17 patients with BRCA1 or BRCA2 mutation and 11 responses in 46 patients who did not have this mutation. However, in December 2011, AstraZeneca announced that a tentative analysis of another phase II study that sees using olaparib to sustain a successful response to platinum-based chemotherapy suggests that the reported growth-free survival benefits are unlikely to translate into overall survival benefits. ; olaparib will not advance to phase III of development, and AstraZeneca takes a cost of $ 285 million. However, the planned analysis of a subset that has a BRCA mutation finds a clear advantage with olaparib, which renews interest. Thus, two phase III trials were initiated on BRCA ovarian cancer mutated in 2013.
Approval and indication
In December 2014, the FDA and EMA approved olaparib as monotherapy, with a recommended dosage of 400 mg taken twice daily. FDA approval is in mutated BRCA germline (gBRCAm) advanced ovarian cancer that has received three or more previous chemotherapy lines. The EMA public assessment report, which uses the same Phase II trial data, refers to "high levels of ovarian cancer" and the use of olaparib "not later than 8 weeks after platinum-based drugs, when the tumor is reduced in size or has completely disappeared ", reflecting a phase II trial of olaparib as a maintenance therapy for serous platinum-sensitive platinum serous carcinoma.
In breast cancer, olaparib is approved for HER2-negative gBRCAm metastatic breast cancer patients who have previously been treated with chemotherapy in neoadjuvant, adjuvant or metastatic settings. If the patient has positive hormone receptor cancer, they should receive endocrine therapy if necessary. This approval is based on trials of the Olympiad III random phase, which shows the benefits of progression-free survival for patients treated with olaparib compared with conventional chemotherapy.
Side effects
Side effects include gastrointestinal effects such as nausea, vomiting, and loss of appetite; fatigue; muscle and joint pain; and low blood counts such as anemia, with occasional leukemia. Somnolen is sometimes seen in clinical trials that use doses higher than the approved schedule.
References
Source of the article : Wikipedia
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