Lynparza

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; 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 & 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 adults 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 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 & have previously been treated w/ anthracycline & taxane in the (neo)adjuvant or metastatic setting unless unsuitable 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. Metastatic castration-resistant prostate cancer (mCRPC) & BRCA1/2-mutations (germline &/or somatic) in adults who have progressed following a prior therapy that included new hormonal agent. In combination w/ abiraterone & prednisone or prednisolone for adults 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. Total daily dose: 600 mg. Monotherapy Patient 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. Duration of treatment: Maintenance treatment of BRCA-mutated advanced ovarian cancer; 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 adverse reactions 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 dose 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).

Discontinue use if myelodysplastic syndrome &/or AML; pneumonitis is confirmed. Not to start treatment until patient has recovered from haematological toxicity caused by previous anticancer therapy (haemoglobin, platelet & neutrophil levels should be ≤CTCAE grade 1). Interrupt treatment & initiate appropriate haematological testing if severe haematological toxicity or blood transfusion dependence develops; prompt investigation if new or worsening resp symptoms (eg, dyspnoea, cough & fever) or abnormal chest radiologic finding is observed. Perform baseline testing, followed by mthly monitoring of CBC for the 1st 12 mth of treatment & periodically after; bone marrow analysis &/or blood cytogenetic analysis if blood parameters remain clinically abnormal after 4 wk of dose interruption. Monitor patients for clinical signs & symptoms of venous thrombosis & pulmonary embolism; w/ prior history of VTE. Not recommended for co-administration w/ strong or moderate CYP3A inhibitors & inducers. 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 should perform pregnancy test prior to & regularly during treatment; must use 2 forms of reliable contraception prior to initiation, during therapy & for 6 mth after receiving the last dose. Male patients w/ pregnant or childbearing potential partners must use a condom & should not donate sperm during therapy & for 3 mth after receiving the last dose. Not to be used during pregnancy. Use during breast-feeding & for 1 mth after receiving the last dose is contraindicated. 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. Co-administration 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. Not recommended for concomitant use w/ grapefruit juice; strong CYP3A inducers (eg, efavirenz, rifabutin). Decreased mean C_max & AUC w/ strong CYP3A inducers eg, phenytoin, rifampicin, rifapentine, carbamazepine, nevirapine, phenobarb & St. John's wort. 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). Reduced exposure to substrates of CYP1A2, 2B6 & 3A4, CYP2C9, CYP2C19 & P-gp. Reduced efficacy of some hormonal contraceptives. Increased exposure to BCRP substrates (eg, MTX, rosuvastatin), OATP1B1 (eg, bosentan, glibenclamide, repaglinide, statins & valsartan), OCT1 (eg, metformin), OCT2 (eg, serum creatinine), OAT3 (eg, furosemide & MTX), MATE1 & 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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