Lynparza

Olaparib

Monotherapy for the maintenance treatment of adults w/ advanced (FIGO stages III & IV) BRCA1/2-mutated (germline &/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response following completion of 1st-line platinum-based chemotherapy. Monotherapy for the maintenance treatment of adults w/ platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In combination w/ bevacizumab for the maintenance treatment of adults w/ advanced (FIGO stages III & IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response following completion of 1st-line platinum-based chemotherapy in combination w/ bevacizumab & whose cancer is associated w/ homologous recombination deficiency (HRD) +ve status defined by either a BRCA1/2 mutation &/or genomic instability. Monotherapy or in combination w/ endocrine therapy for the adjuvant treatment of adults w/ germline BRCA1/2-mutations who have HER2 -ve, high risk early breast cancer previously treated w/ neoadjuvant or adjuvant chemotherapy. Monotherapy for the treatment of adults w/ germline BRCA1/2-mutations, who have HER2 -ve locally advanced or metastatic breast cancer, in which patients should have previously been treated w/ an anthracycline & a taxane in the (neo)adjuvant or metastatic setting unless not suitable for these treatments; patients w/ hormone receptor (HR) +ve breast cancer should also have progressed on or after prior endocrine therapy, or be considered unsuitable for endocrine therapy. Monotherapy for the maintenance treatment of adults w/ germline BRCA1/2-mutations who have metastatic adenocarcinoma of the pancreas & have not progressed after a min of 16 wk of platinum treatment w/in a 1st-line chemotherapy regimen. Monotherapy for the treatment of adults w/ metastatic castration-resistant prostate cancer (mCRPC) & BRCA1/2-mutations (germline &/or somatic) who have progressed following prior therapy that included a new hormonal agent. In combination w/ abiraterone & prednisone or prednisolone for the treatment of adults w/ mCRPC in whom chemotherapy is not clinically indicated.

300 mg (two 150-mg tab) bd. Monotherapy for patients w/ platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy Start treatment no later than 8 wk after completion of final dose of the platinum-containing regimen. 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer; 1st-line maintenance treatment of HRD +ve advanced ovarian cancer in combination w/ bevacizumab Continue treatment until radiological disease progression, unacceptable toxicity or for up to 2 yr if there is no radiological evidence of disease after 2 yr of treatment. Patients w/ evidence of disease at 2 yr can be treated beyond 2 yr. Maintenance treatment of platinum-sensitive relapsed ovarian cancer; monotherapy of gBRCA1/2-mutated HER2 -ve metastatic breast cancer; 1st-line maintenance treatment of gBRCA-mutated metastatic adenocarcinoma of the pancreas; monotherapy of BRCA1/2-mutated metastatic castration-resistant prostate cancer; treatment of mCRPC in combination w/ abiraterone & prednisone or prednisolone Continue treatment until progression of the underlying disease or unacceptable toxicity. Adjuvant treatment of germline BRCA-mutated high risk early breast cancer Up to 1 yr, or until disease recurrence, or unacceptable toxicity, whichever occurs 1st. Patient w/ moderate renal impairment (CrCl 31-50 mL/min) 200 mg (two 100-mg tab) bd.

May be taken with or without food: Swallow whole, do not chew/crush/dissolve/divide.

Hypersensitivity. Breast-feeding during treatment & for 1 mth after the last dose.

Haematological toxicity. Perform baseline testing, followed by mthly monitoring, of CBCs for the 1st 12 mth of treatment & periodically thereafter. Myelodysplastic syndrome/AML. Venous thromboembolic events. Pneumonitis. Not recommended w/ strong or moderate CYP3A inducers or inhibitors. Moderate influence on the ability to drive & use machines. Not recommended in patients w/ severe renal impairment or ESRD (CrCl ≤30 mL/min); severe hepatic impairment (Child-Pugh C). Can cause foetal harm. Do not use during pregnancy. Women of childbearing potential must use 2 forms of reliable contraception before starting therapy, during therapy & for 6 mth after receiving the last dose. Male patients & their female partners of childbearing potential must use reliable contraception during therapy & for 3 mth after receiving the last dose. Safety & efficacy in childn & adolescents have not been established.

Anaemia, neutropenia, leukopenia; decreased appetite; dizziness, headache, dysgeusia; cough, dyspnoea; vomiting, diarrhoea, nausea, dyspepsia; fatigue (including asthenia). Lymphopenia, thrombocytopenia; stomatitis, upper abdominal pain; rash; increased blood creatinine; VTE.

Potentiated & prolonged myelosuppressive toxicity w/ other anticancer medicinal products, including DNA-damaging agents. Caution w/ vaccines or immunosuppressant agents. Increased mean C_max & mean AUC w/ strong (eg, itraconazole, telithromycin, clarithromycin, ritonavir- or cobicistat-boosted PIs, boceprevir, telaprevir) or moderate (eg, erythromycin, diltiazem, fluconazole, verapamil) CYP3A inhibitors. Not recommended w/ grapefruit juice. Decreased mean C_max & mean AUC w/ strong CYP3A inducers (eg, phenytoin, rifampicin, rifapentine, carbamazepine, nevirapine, phenobarb, St. John's wort). Not recommended w/ moderate to strong CYP3A inducers (eg, efavirenz, rifabutin). Increased exposure of sensitive CYP3A substrates or substrates w/ narrow therapeutic index (eg, simvastatin, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, sirolimus, tacrolimus, quetiapine); substrates of BCRP (eg, MTX, rosuvastatin), OATP1B1 (eg, bosentan, glibenclamide, repaglinide, statins, valsartan), OCT1 (eg, metformin), OCT2 (eg, serum creatinine), OAT3 (eg, furosemide, MTX), MATE1 (eg, metformin) & MATE2K (eg, metformin). May reduce exposure of CYP2B6, CYP2C9, CYP2C19 & P-gp substrates. May reduce efficacy of some hormonal contraceptives. May cause clinically relevant drug interactions w/ P-gp substrates (eg, simvastatin, pravastatin, dabigatran, digoxin, colchicine).

Targeted Cancer Therapy

L01XK01 - olaparib ; Belongs to the class of poly (ADP-ribose) polymerase (PARP) inhibitors. Used in the treatment of cancer.

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