Lynparza

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 complete or partial response 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 complete or partial response 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 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 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. Monotherapy or in combination w/ endocrine therapy for the adjuvant treatment of adult patients w/ germline BRCA1/2 mutations who have HER2 -ve high risk early breast cancer who have previously treated w/ neoadjuvant or adjuvant chemotherapy; 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. Treatment of adult patients w/ metastatic castration-resistant prostate cancer (mCRPC) & BRCA1/2-mutations (germline &/or somatic) who have progressed following a prior therapy that included new hormonal agent; combination w/ abiraterone & prednisone or prednisolone for treatment of adult patients w/ mCRPC in whom chemotherapy is not clinically indicated.

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. Duration of treatment: Maintenance treatment of BRCA-mutated advanced ovarian cancer; 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. Patient 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; maintenance treatment of gBRCA-mutated metastatic adenocarcinoma of the pancreas; HRR-gene mutated metastatic castration-resistant prostate cancer; monotherapy treatment of BRCA1/2-mutated mCRPC; 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. Dose adjustments for AR May reduce dose 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 if w/ strong CYP3A inhibitor or 150 mg twice daily if w/ moderate CYP3A inhibitor. Moderate renal impairment (CrCl 31-50 mL/min) Recommended dose: 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. Perform baseline testing, followed by mthly monitoring of CBC for the 1st 12 mth of treatment & periodically after. 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. Monitor patients for clinical signs & symptoms of venous thrombosis & pulmonary embolism & treat as medically appropriate; w/ prior history of VTE. Interrupt treatment & initiate prompt investigation if new or worsening resp symptoms (eg, dyspnoea, cough & fever) or abnormal chest radiologic finding is observed. Co-administration w/ strong or moderate CYP3A inhibitors or inducers is not recommended. Moderate influence on the ability to drive & use machines. Not recommended in severe renal impairment or ESRD (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 6 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. Childn & adolescents.

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. Closely monitor patients co-administered w/ vaccines or immunosuppressants. Increased mean C_max & AUC w/ strong CYP3A inhibitors (eg, itraconazole, telithromycin, clarithromycin, PIs boosted w/ ritonavir or cobicistat, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg, erythromycin, diltiazem, fluconazole, verapamil). Avoid 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 reduce efficacy of some hormonal contraceptives. May increase exposure to 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).

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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