Lynparza (olaparib) is an FDA-approved poly ADP-ribose polymerase (PARP) inhibitor developed by AstraZeneca for the treatment of advanced ovarian cancer.

It is currently being studied in clinical trials for certain types of breast cancer.

How Lynparza works

During the normal aging process, cells accumulate damage in their genetic material (DNA) and eventually die. Tumor cells, however, evade cellular death and are able to trigger cell proliferation by using a multiway mechanism to repair the damaged DNA. PARPs are enzymes that aid the DNA repair mechanism.

Cancer cells that have a mutation in the BRCA gene are deficient in some elements of the DNA repair mechanism and are especially reliant on PARP to remain alive.

Lynparza inhibits or prevents the action of the PARP enzymes, which, in combination with the deficiencies in the DNA repair mechanism of BRCA-mutated cells, triggers tumor cell death caused by the excessive accumulation of damage to DNA.

Lynparza in clinical trials

A Phase 3 placebo-controlled study (NCT02000622) to compare the safety and effectiveness of Lynparza to that of standard chemotherapy for the treatment of metastatic breast cancer patients with germline BRCA1/2 mutations is currently ongoing.

The study, called OlympiAD, includes 302 women who are receiving either Lynparza (300 mg twice daily) or standard chemotherapy such as Xeloda (capecitabine), Navelbine (vinorelbine), and Halaven (eribulin).

The results so far have shown that Lynparza reduces the risk of cancer growth by as much as 42 percent compared to standard chemotherapy treatment. In addition, in 60 percent of patients treated with Lynparza, the tumor shows evident shrinkage. Similar shrinkage is registered in only 29 percent of women on standard chemotherapy. Lynparza also showed fewer side effects compared to standard chemotherapy.

For women on standard chemotherapy, disease progression occurred within 4.2 months, while in women treated with Lynparza, it took seven months for disease progression to occur.

Two clinical trials are currently recruiting breast cancer patients to further test Lynparza. One is a placebo-controlled Phase 3 study called OlympiA (NCT02032823), which is assessing the safety and effectiveness of Lynparza as an adjuvant treatment in patients with germline BRCA1/2 mutations breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. The trial expects to enroll up to 1,500 participants

The second trial, called PARTNER (NCT03150576), is a randomized Phase 2/3 study evaluating the safety and efficacy of the addition of Lynparza to platinum-based neoadjuvant chemotherapy in breast cancer patients with germline BRCA-mutations. This trial expects to enroll 527 participants.

Other information

The most common adverse reactions to Lynparza treatment are anemia, nausea, fatigue, vomiting, diarrhea, loss of sense of taste, indigestion, headache, decreased appetite, cough, rash, and pain in the muscles, bones, back, and abdomen.

Lynparza is currently approved in the U.S. as monotherapy in patients with germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The drug is also approved by the European Medicines Agency (EMA) as a monotherapy for the treatment of patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are responsive to platinum-based chemotherapy.


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