Page 1 of 5 Indication Treatment Intent Frequency and number of cycles Monitoring parameters pre-treatment The neoadjuvant treatment of locally advanced, inflammatory or early HER2 positive breast cancer at high risk of recurrence (stage T2-T4b and M0). Patients should have received no prior treatment with chemotherapy or HER2 therapy for this breast cancer. Neo-adjuvant Every 3 weeks 3 cycles of FEC followed by 4 cycles docetaxel, pertuzumab and trastuzumab (iv) followed by 14 cycles trastuzumab (iv or sc) alone FEC ECG should be checked prior to cycle 1 (see ongoing cardiac monitoring below during pertuzumab & trastuzumab treatment). Monitor FBC, LFT and U&E at each cycle Consider dose reduction in renal or hepatic impairment If neuts <1 or PLT <100 d/w consultant. If neuts > 1 and PLT> 100 continue with treatment Dose reduction should be considered if grade 3 or 4 non-haematological toxicity or repeat appearance of grade 2 (except N&V and alopecia). Delay until resolution of toxicity to < grade 1 Docetaxel, Pertuzumab and The use of trastuzumab and pertuzumab is restricted to patients whose tumours significantly overexpress HER2 at the 3+ level by IHC or FISH/CISH positive disease. must not be given within 3 weeks of an anthracycline, therefore it must be started a minimum of 3 weeks after administration of the final dose of anthracycline therapy. Ensure Dexamethasone pre-medication (8mg bd for 3 days starting day before docetaxel) is prescribed and given to the patient on cycle 3 of FEC. At each nurse assessment, patients should be assessed for signs of dyspnoea. If the first trastuzumab(iv) dose is well tolerated (no infusion related reactions), then the second and subsequent doses may be administered over the shorter infusion time of 30 minutes. If pertuzumab is well tolerated on cycle 1 (no infusion related reactions), then the second and subsequent doses may be administered over the shorter infusion time of 30 minutes. If not then, continue to administer subsequent doses over 60 minutes. Observations should be taken every 30 minutes during the pertuzumab infusion and patients should be monitored for 1 hour after the infusion before starting trastuzumab. Patients must be observed closely for infusion related adverse effects for 6 hours after the start of the loading dose of trastuzumab (iv), 2 hours after the start of the second dose of trastuzumab (iv) and one hour after the start of subsequent doses (if trastuzumab sc is given for maintenance, patients must be observed closely for infusion related adverse effects for 30 mins after the injection). FBC, U&Es and LFTs at each cycle of docetaxel, pertuzumab and trastuzumab, and then FBC every 3 months, ie pre the 1 st, 5 th, 9 th, and 13 th dose of maintenance trastuzumab to correspond with pre cycle 8,12, 16 and 20 of the regimen. Prior to each cycle of docetaxel, pertuzumab and trastuzumab, if neuts <1.0 or PLT <100 d/w consultant. If neuts >/= 1 and PLT >/=100 continue with treatment. Consider dose reduction of docetaxel in hepatic impairment. Docetaxel is not recommended in severe hepatic impairment. Dose reductions of pertuzumab are not required in mild to moderate renal impairment. There are no recommendations for dose reductions of pertuzumab in severe renal impairment or hepatic impairment. There are no recommendations for dose adjustments of trastuzumab in renal or hepatic impairment. Dose reductions of docetaxel should be considered if grade 3 or 4 non-haematological toxicity or repeat appearance of grade 2 (except N&V and alopecia). Delay until resolution of toxicity to < grade 1. Pertuzumab and trastuzumab should not be reduced. If trastuzumab treatment is discontinued, pertuzumab should also be discontinued. Docetaxel may be escalated to 100mg/m 2 at clinician discretion (see regimen plan for details) If the patient misses a dose of (iv) by more than one week, a re-loading dose of trastuzumab (iv) should be given over 90 minutes. If the time between two sequential infusions of
Page 2 of 5 pertuzumab is 6 weeks or more, the initial loading dose of 840 mg should be re-administered as a 60 minute intravenous infusion followed every 3 weeks thereafter by a maintenance dose of 420 mg administered over a period of 30 to 60 minutes. Cardiac function must be monitored. An ECHO/ MUGA should be carried out at the following timepoints: o Pre cytotoxic chemotherapy (if indicated) o Pre cycle 4 (ie pre-trastuzumab) o Pre cycle 8 o Pre cycle 13 o Pre cycle 18 o 3-4 weeks after the end of treatment Record on KOMs Cardiac Monitoring Record Baseline LVEF must be >/= 55% It is the prescribers responsibility to check that the ECHO/MUGA result is satisfactory before continuing treatment. In the event of left ventricular dysfunction, pertuzumab and trastuzumab should be withheld for at least 3 weeks for any of the following: signs and symptoms of CHF, a drop in LVEF to less than 40%, a LVEF of 40%-45% associated with a fall of 10% points below pre-treatment values. Pertuzumab and trastuzumab may be resumed if the LVEF has recovered to >/= 45%. If after a repeat assessment within approximately 3 weeks, the LVEF has not improved, or has declined further, discontinuation of pertuzumab and trastuzumab should be strongly considered, unless the benefits for the individual patient are deemed to outweigh the risks. Reference(s) SpC Pertuzumab and trastuzumab accessed 24/11/16 Schneeweiss A et al Ann Oncol (2013) 24 (9): 2278-2284. NHSE CDF list accessed on line 24/11/16 NB For funding information, refer to the SACT funding spreadsheet
Page 3 of 5 Day / Cycle Drug Dose Route Dexamethasone 8mg po Ondansetron <75yrs >75yrs 16mg 8mg Infusion Duration EPIRUBICIN (100mg/m²) IV slow bolus 5-FLUOROURACIL (500mg/m²) Administration Details IV 15 min Sodium chloride 0.9% 50ml IV slow bolus CYCLOPHOSPHAMIDE IV slow bolus (600mg/m²) TTO Drug Dose Route Directions Cycles 3 only Metoclopramide 10mg po up to 3 times a day for 3 days, then 10mg up to 3 times a day as required Ondansetron 8mg po bd for 3 days Dexamethasone 6mg po om for 3 days Filgrastim 300 micrograms or od starting on day 5 for 5 days consider dose of 480 sc micrograms if patient > 80kg Dexamethasone 8mg po bd for 3 days, starting day before docetaxel
Page 4 of 5 Cycles 4-7 Day / cycle Drug Dose Route Cycle 4 Cycle 4 Day 2 Cycles 5-7 Infusion Duration Administration Details Pertuzumab loading dose 840mg IV 60 min In 250ml sodium chloride 0.9% Observations should be taken every 30 minutes during the pertuzumab infusion and patients should be monitored for 1 hour after the infusion before starting trastuzumab 8mg/kg IV 90 min In 250ml sodium chloride 0.9% loading dose Patients must be observed closely for infusion related adverse effects for 6 hours after the start of trastuzumab Please ensure dexamethasone pre-med has been taken prior to administration of chemotherapy Metoclopramide 20mg IV DOCETAXEL 75mg/m 2 IV 1 hr Sodium Chloride 0.9% 250ml Pertuzumab maintenance dose 420mg IV 30-60 mins see monitoring parameters In 250ml sodium chloride 0.9% Observations should be taken every 30 minutes during infusion and patients should be monitored for one hour after infusion before starting trastuzumab maintenance dose 6mg/kg IV Over 30 mins if tolerated (see monitoring parameters) In 250ml sodium chloride 0.9% Start docetaxel after the end of the trastuzumab observation period (ie 2 hours after the start of the trastuzumab for cycle 5, then one hour from the start of the infusion for cycle 6 onwards). Please ensure dexamethasone pre-med has been taken prior to administration of chemotherapy Metoclopramide 20mg IV DOCETAXEL *The dose of docetaxel can be increased from 75mg/m 2 to 100mg/m² from cycle 5 onwards if patient is able to tolerate an increase in dose. 75mg/m 2 * IV 1 hr Sodium Chloride 0.9% 250ml TTO MEDICATION Cycles 4-7 Metoclopramide 10mg po Cycles 4, 5 & 6 only Drug Dose Route Directions up to 3 times a day for 3 days after docetaxel, then 10mg up to 3 times a day as required (max. 30mg per day including 20mg prechemo dose) Co-codamol 30/500 1-2 tablets po qds when required for pain Filgrastim 300 micrograms or consider dose of 480 micrograms if patient > 80kg Loperamide Dexamethasone 8mg po sc po od starting the day after docetaxel for 7 days Take 4mg initially then 2mg after each loose stool when required (max. 16mg per day). Dispense original pack on cycle 4 then only if required. bd for 3 days, starting day before next cycle of chemotherapy
Page 5 of 5 Cycles 8-21 Day Drug Dose Route Infusion Duration Administration Details 1 Maintenance dose 6mg/kg IV Over 30 mins if tolerated (see monitoring parameters) In 250ml sodium chloride 0.9% ALTERNATIVELY trastuzumab may be given sub cutaneously from cycle 8 21 as below Day Drug Dose Route Infusion Duration Administration Details 1 Maintenance dose 600mg Sub cut Over 2-5 mins Alternate injection site between the right and left thigh at least 2.5cm away from the previous injection site.