Lynparza

Olaparib

Ovarian cancer: Monotherapy for the maintenance treatment of adult patients 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 response (complete or partial) following completion of 1st-line platinum-based chemotherapy; w/ platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. In combination w/ bevacizumab for the maintenance treatment of adult patients w/ advanced (FIGO stages III & IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) 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. Adenocarcinoma of the pancreas: Monotherapy for the maintenance treatment of adult patients w/ deleterious or suspected deleterious germline BRCA1/2-mutations who have metastatic adenocarcinoma of the pancreas & have not progressed on at least 16 wk of a 1st-line platinum based chemotherapy regimen. Breast cancer: Monotherapy for the treatment of adult patients w/ germline BRCA1/2 mutations, who have HER2 -ve locally advanced or metastatic breast cancer. Patients should have previously been treated w/ an anthracycline & a taxane in the (neo)adjuvant or metastatic setting unless patients were 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. Prostate cancer: Treatment of adult patients w/ metastatic castration-resistant prostate cancer & BRCA1/2-mutations (germline &/or somatic) who have progressed following a prior therapy that included new hormonal agent.

Recommended dose (in monotherapy or in combination w/ bevacizumab): 300 mg (two 150 mg tab) twice daily equiv to a total daily dose of 600 mg. Monotherapy Patient w/ platinum-sensitive relapsed (PSR) high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy Start treatment no later than 8 wk after completion of final dose of the platinum-containing regimen. In combination w/ bevacizumab 15 mg/kg bevacizumab once every 3 wk. Duration of treatment: Maintenance treatment of BRCA-mutated advanced ovarian cancer 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. Patient w/ evidence of disease at 2 yr can be treated beyond 2 yr. Maintenance treatment of platinum sensitive relapsed ovarian cancer & gBRCA1/2 mutated HER2 -ve metastatic breast cancer, gBRCA-mutated metastatic adenocarcinoma of the pancreas, HRR-gene mutated metastatic castration-resistant prostate cancer Continue treatment until progression of the underlying disease or unacceptable toxicity. BRCA1/2-mutated metastatic castration-resistant prostate cancer Continue treatment until progression of underlying disease or unacceptable toxicity. Medical castration w/ luteinising LHRH analogue should be continued during treatment in patients not surgically castrated. 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. Dose adjustments for AR Reduce to 250 mg twice daily or further dose reduction to 200 mg twice daily may be considered. Dose adjustments for co-administration w/ CYP3A inhibitor Reduce to 100 mg twice daily w/ strong CYP3A inhibitor or 150 mg twice daily w/ moderate CYP3A inhibitor. Moderate renal impairment (CrCl 31-50 mL/min) 200 mg twice daily.

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

Hypersensitivity. Breast-feeding (during treatment & 1 mth after last dose).

Do not start treatment until patient has recovered from haematological toxicity caused by previous anticancer therapy. Baseline testing, followed by mthly monitoring of CBC is recommended for the 1st 12 mth of treatment & periodically after this time. Interrupt treatment & initiate appropriate haematological testing if severe haematological toxicity or blood transfusion dependence develops. Bone marrow analysis &/or blood cytogenetic analysis are recommended if blood parameters remain clinically abnormal after 4 wk of dose interruption. Discontinue use if myelodysplastic syndrome &/or acute myeloid leukaemia; pneumonitis are confirmed. Interrupt treatment if new or worsening resp symptoms (eg, dyspnoea, cough & fever) or an abnormal chest radiologic finding is observed. Co-administration w/ strong or moderate CYP3A inhibitors & inducers is not recommended. Moderate influence on the ability to drive & use machines. Not recommended in severe renal impairment or end-stage renal disease (CrCl ≤30 mL/min) & severe hepatic impairment (Child-Pugh class C). May cause foetal harm. Women of childbearing potential must use 2 forms of reliable contraception prior to initiation, during therapy & for 1 mth after receiving the last dose. Male patients must use a condom & should not donate sperm during therapy & for 3 mth after receiving the last dose. Not to be used during pregnancy. Contraindicated during breast-feeding & for 1 mth after receiving the last dose. Childn & adolescents.

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

Potentiation & prolongation of myelosuppressive toxicity w/ other anticancer drugs including DNA damaging agents. Closely monitor patients co-administered w/ vaccines or immunosuppressants. Increased mean C_max & AUC w/ strong (eg, itraconazole, telithromycin, clarithromycin, PIs boosted w/ ritonavir or cobicistat, boceprevir, telaprevir) or moderate (eg, erythromycin, diltiazem, fluconazole, verapamil) CYP3A inhibitors. Grapefruit juice. Decreased mean C_max & 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). Clinical monitoring w/ CYP3A substrates or substrates w/ narrow therapeutic margin (eg, simvastatin, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, sirolimus, tacrolimus & quetiapine) & P-gp substrates (eg, simvastatin, pravastatin, dabigatran, digoxin & colchicine). May reduce exposure to substrates of CYP1A2, 2B6 & 3A4, CYP2C9, CYP2C19 & P-gp substrates. May increase exposure to substrates of BCRP (eg, methotrexate, rosuvastatin), OATP1B1 (eg, bosentan, glibenclamide, repaglinide, statins & valsartan), OCT1 (eg, metformin), OCT2 (eg, serum creatinine), OAT3 (eg, furosemide & methotrexate), MATE1 (eg, metformin) & MATE2K (eg, metformin). Decreased exposure w/ tamoxifen.

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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