Lynparza

Olaparib

Hard cap: Monotherapy for maintenance treatment of adult patients w/ platinum-sensitive relapsed BRCA-mutated (germline &/or somatic) high-grade serous ovarian (including fallopian tube or primary peritoneal) cancer who are in complete or partial response to platinum-based chemotherapy. FC tab: Monotherapy for 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 as 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. Adjuvant treatment of adult patients w/ germline BRCA-mutated (gBRCAm) HER2 -ve high risk early breast cancer who have previously been treated w/ neoadjuvant or adjuvant chemotherapy. Monotherapy for adult patients w/ gBRCAm HER2 -ve metastatic breast cancer who have been previously treated w/ chemotherapy. Monotherapy for maintenance treatment of adult patients w/ deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on a min of 16 wk of 1st-line platinum-based chemotherapy. Monotherapy for adult patients w/ metastatic castration-resistant prostate cancer & homologous recombination repair gene BRCA1/2 &/or ataxia telangiectasia mutations (germline &/or somatic) who have progressed following a prior new hormonal agent.

Hard cap Start treatment no later than 8 wk after completion of final dose of the platinum-containing regimen. Adult Recommended dose: 400 mg (eight 50 mg cap) bd equiv to a total daily dose of 800 mg. Dose adjustments for adverse events May reduce dose to 200 mg bd or further reduce to 100 mg bd. Dose adjustments for co-administration w/ CYP3A inhibitor Reduce dose to 150 mg bd if w/ strong CYP3A inhibitor; 200 mg bd if w/ moderate CYP3A inhibitor. Moderate renal impairment (CrCl 31-50 mL/min) Recommended dose: 300 mg bd. FC tab Adult Recommended dose: 300 mg (two 150 mg tab) bd equiv to a total daily dose of 600 mg. Monotherapy maintenance treatment of newly diagnosed advanced BRCA-mutated ovarian cancer, 1st-line maintenance treatment of HRD +ve advanced ovarian cancer in combination w/ bevacizumab Duration of treatment: Can continue for 2 yr or until disease progression; should be stopped at 2 yr in patients w/ complete response (no radiological evidence of disease); can be treated beyond 2 yr in patients w/ evidence of disease at 2 yr, who in the opinion of the treating physician can derive further benefit from continuous treatment. Adjuvant treatment of gBRCAm HER2 -ve high risk early breast cancer Duration of treatment: Can be treated for a total of 1 yr or until disease recurrence or unacceptable toxicity whichever occurs first. Platinum-sensitive relapsed ovarian cancer, metastatic HER2 -ve breast cancer & maintenance following 1st-line treatment of metastatic pancreatic adenocarcinoma, HRR-gene BRCA1/2 &/or ATM-mutated metastatic castration-resistant prostate cancer Duration of treatment: Continue until progression of the underlying disease. Dose adjustments for adverse events May reduce dose to 250 mg bd or further reduce to 200 mg bd. Dose adjustments for co-administration w/ CYP3A inhibitor Reduce dose to 100 mg bd if w/ strong CYP3A inhibitor; 150 mg bd if w/ moderate CYP3A inhibitor. Moderate renal impairment (CrCl 31-50 mL/min) Recommended dose: 200 mg bd.

Should be taken on an empty stomach: Take at least 1 hr after meal and refrain from eating for 2 hr after intake.

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. Discontinue use if myelodysplastic syndrome &/or AML; pneumonitis is confirmed. 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 inducers or inhibitors is not recommended. Possible asthenia, fatigue & dizziness; observe caution when driving or using machines. Not recommended for patients w/ severe renal impairment or ESRD (CrCl ≤30 mL/min) & severe hepatic impairment (Child-Pugh class C). May cause foetal harm. Advise women of childbearing potential to use effective contraception during treatment & for 1 mth after receiving the last dose. Not to be taken during pregnancy. Advise not to breastfeed during treatment & for 1 mth after receiving the last dose. Not indicated for childn or adolescents. Elderly ≥75 yr. Hard cap: Possible VTE events including pulmonary embolism; higher incidence observed in patients w/ metastatic castration-resistant prostate cancer who also received androgen deprivation therapy; monitor for signs & symptoms & treat as medically appropriate. FC tab: Female partners of male patients taking Lynparza should avoid pregnancy. Male patients must use a condom & should not donate sperm; & their female partners of childbearing potential must use effective contraception during treatment & for 3 mth after receiving the last dose.

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

Potentiated & prolonged myelosuppressive toxicity w/ other anticancer agents including DNA damaging agents. Increased C_max & AUC w/ itraconazole & other strong CYP3A inhibitors (eg, telithromycin, clarithromycin, PIs boosted w/ ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir & telaprevir). Altered clearance w/ moderate CYP3A inhibitors (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole & verapamil). Avoid grapefruit, grapefruit juice, Seville oranges & Seville orange juice. Decreased C_max & AUC w/ strong CYP3A inducers (eg, phenytoin, rifabutin, rifampin, rifapentine, carbamazepine, nevirapine, phenobarb, St. John's wort). Decreased AUC w/ moderate CYP3A inducers (eg, bosentan, efavirenz, etravirine, modafinil & nafcillin). Sensitive CYP3A substrates or substrates w/ narrow therapeutic margin (eg, simvastatin, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, sirolimus, tacrolimus, quetiapine). May reduce exposure to substrates of CYP1A2 & 2B6 metabolic enzymes. May increase the exposure of substrates of OATP1B1 (eg, bosentan, glibenclamide, repaglinide, statins & valsartan), OCT1 (eg, metformin), OCT2 (eg, serum creatinine), OAT3 (eg, furosemide & MTX), MATE1 (eg, metformin & cisplatin) & MATE2K (eg, metformin). Hard cap: Slowed absorption rate & increased extent of absorption w/ food.

Targeted Cancer Therapy

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

POM