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olaparib (Lynparza)

Indications: - advanced (treatment refractory) ovarian cancer*, fallopian tube cancer or peritoneal cancer with germline BRCA1 mutation or BRCA2 mutation whose disease has responded to platinum based chemotherapy only if: - they have had >=3 courses of platinum based chemotherapy (NGC, NICE) - seems to improve progression-free survival in patients with newly diagnosed advanced ovarian cancer# [5] - metastatic breast cancer with BRCA mutation [4] - metastatic androgen-insensitive prostate cancer [2,7,8] * on list of drugs to avoid for treatment of ovarian cancer [3] - has not been shown to prolong survival # industry-sponsored study Contraindications: - pregnancy (teratogen) - breast feeding Dosage: - tablets: 100 mg, 150 mg Adverse effects: - anemia, neutropenia, leukopenia [4] - fatigue, headache - nausea, vomiting - respiratory tract infections: nasopharyngitis, influenza - dyspepsia, diarrhea, constipation, indigestion, decreased appetite - arthralgia, myalgia) - dysgeusia, stomatitis [4] Complications: - myelodysplastic syndrome/acute myeloid leukemia - pneumonitis Laboratory: - BRACAnalysis CDx Mechanism of action: - inhibits poly ADP-ribose polymerase

General

small inhibitory antineoplastic agent (ib drug) PARP inhibitor

Database Correlations

PUBCHEM cid=23725625

References

  1. FDA News Release. December 19, 2014 FDA approves Lynparza to treat advanced ovarian cancer First LDT companion diagnostic test also approved to identify appropriate patients http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427554.htm
  2. Mateo J et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med 2015 Oct 29; 373:1697 PMID: 26510020 http://www.nejm.org/doi/full/10.1056/NEJMoa1506859
  3. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
  4. FDA News Release. January 12, 2018 FDA approves first treatment for breast cancer with a certain inherited genetic mutation. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm592347.htm
  5. Moore K, Colombo N, Scambia G et al Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Eng J Med. Oct 21, 2018 PMID: 30345884 Free Article https://www.nejm.org/doi/full/10.1056/NEJMoa1810858
  6. Kaufman B, Shapira-Frommer R, Schmutzler RK et al Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. PMID: 25366685 Free PMC Article
  7. de Bono J, Mateo J, Fizazi K et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med 2020; 382:2091-2102. May 28. PMID: 32343890 https://www.nejm.org/doi/10.1056/NEJMoa1911440
  8. Hussain M et al. Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med 2020 Sep 20; [e-pub]. PMID: 32955174 https://www.nejm.org/doi/10.1056/NEJMoa2022485
  9. Medscape: olaparib (Rx) https://reference.medscape.com/drug/lynparza-olaparib-999934