Indication(s):

Monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer who have been treated with ≥3 prior lines of chemotherapy.

Pharmacology:

Olaparib inhibits poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, PARP3. It has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth in mouse xenograft models of human cancer both as monotherapy or following platinum-based chemotherapy.

In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasis and cell death.

Clinical Trials:

The efficacy of Lynparza was eva luated in a single-arm study involving 137 patients with germline BRCA-mutated (gBRCAm) advanced cancers who had been treated with ≥3 prior lines of chemotherapy. All patients received Lynparza 400mg twice daily as monotherapy until disease progression or intolerable toxicity. The objective response rate (ORR) and duration of response (DOR) were assessed by the investigator.

Study results showed an ORR of 34% (95% CI: 26, 42) with a complete response in 2% of patients, and a partial response in 32% of patients. The median DOR was 7.9 months (95% CI: 5.6, 9.6).

Legal Classification:

Rx

Adults:

Swallow capsules whole. 400mg twice daily; max 800mg daily. Continue until disease progression or unacceptable toxicity. Dose adjustments for adverse reactions: reduce to 200mg twice daily; may further reduce to 100mg twice daily. If concomitant strong CYP3A inhibitor unavoidable: reduce to 150mg twice daily; or if concomitant moderate CYP3A inhibitor unavoidable: reduce to 200mg twice daily.

Children:

Not established.

Warnings/Precautions:

Monitor CBC at baseline and monthly thereafter; do not start therapy until recovery from hematological toxicity due to previous chemotherapy (CTCAE Grade ≤1). Discontinue if myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) is confirmed. Interrupt therapy and eva luate if new or worsening respiratory symptoms occur; discontinue if pneumonitis is confirmed. Hepatic and moderate-to-severe renal impairment: not studied. Pregnancy (Category D); avoid. Use effective contraception during therapy and for at least 1 month after last dose. Nursing mothers: not recommended.

Interaction(s)

Increased myelosuppressive toxicity with concomitant other myelosuppressive anticancer agents, including DNA damaging agents. Avoid concomitant strong CYP3A inhibitors (eg, itraconazole, telithromycin, clarithromycin, ketoconazole, voriconazole, nefazodone, posaconazole, ritonavir, lopinavir/ritonavir, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) and moderate CYP3A inhibitors (eg, amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil); if unavoidable, reduce dose (see Adults). Avoid grapefruit and Seville oranges. Avoid concomitant strong CYP3A inducers (eg, phenytoin, rifampicin, carbamazepine, St. John’s Wort) and moderate CYP3A inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin); if unavoidable, be aware of potential for decreased efficacy.

Adverse Reaction(s)

Anemia, nausea, fatigue, asthenia, vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/URI, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, abdominal pain/discomfort; lab abnormalities (see full labeling), MDS/AML, pneumonitis.

How Supplied:

Caps—112

LAST UPDATED:

2/13/2015