Lynparza

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 (ATM)-mutations (germline &/or somatic) who have progressed following a prior new hormonal agent. In combination w/ abiraterone & prednisone or prednisolone for adult patients w/ metastatic castration-resistant prostate cancer in whom chemotherapy is not clinically indicated. In combination w/ durvalumab as maintenance treatment of adult patients w/ advanced or recurrent endometrial cancer that is mismatch repair proficient (pMMR) whose disease has not progressed on 1st-line treatment w/ durvalumab in combination w/ carboplatin & paclitaxel.

Adult Monotherapy or in combination w/ other agents 300 mg (two 150 mg tab) bd equiv to 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 & monotherapy of HRR-gene BRCA1/2 &/or ATM-mutated metastatic castration-resistant prostate cancer Duration of treatment: Continue until progression of the underlying disease. Metastatic castration-resistant prostate cancer in combination w/ abiraterone & prednisone or prednisolone & 1st-line maintenance treatment of advanced or recurrent endometrial cancer in combination w/ durvalumab Duration of treatment: Continue until progression of the underlying disease or unacceptable toxicity. 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) 200 mg bd.

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

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 pure red cell aplasia (PRCA) or autoimmune haemolytic anaemia is confirmed when used in combination w/ durvalumab. 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 clinical signs & symptoms & treat as medically appropriate. Discontinue use & treat appropriately 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. Interrupt treatment if drug-induced liver injury is suspected & discontinue use if it is confirmed. 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 6 mth after receiving the last dose. 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. 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.

Monotherapy: Anaemia, neutropenia, leukopenia; decreased appetite; dizziness, headache, dysgeusia; cough, dyspnoea; vomiting, diarrhoea, nausea, dyspepsia; fatigue (including asthenia). Thrombocytopenia, lymphopenia; stomatitis, upper abdominal pain; rash; increased blood creatinine, VTE. In combination w/ durvalumab: PRCA.

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). Concomitant use w/ 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).

Targeted Cancer Therapy

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

POM