Pertuzumab (Specialist drug)

PATIENT SELECTION: patients must have HER2-positive tumour status (IHC score 3+ and/or ISH ratio at least 2.0) assessed by a validated test. ADMINISTRATION: an observation period of 30-60 minutes is recommended after completion of each infusion and must be completed before any subsequent infusion of trastuzumab or chemotherapy. Pertuzumab and trastuzumab are given sequentially and may be given in any order; in patients receiving a taxane, both are given before the taxane. If the first infusion is well tolerated, subsequent infusions may be given over 30 to 60 minutes. COMBINATION PARTNERS (as stated in the SPC): trastuzumab on a 3-weekly schedule, either IV with a loading dose of 8 mg/kg body weight then 6 mg/kg every 3 weeks, or a fixed subcutaneous dose of 600 mg every 3 weeks irrespective of body weight; docetaxel may start at 75 mg/m2 and be escalated to 100 mg/m2 depending on regimen and tolerability, or be given at 100 mg/m2 3-weekly from the start (75 mg/m2 throughout with no escalation if a carboplatin-based regimen is used); in the adjuvant setting paclitaxel 80 mg/m2 once weekly for 12 weekly cycles. In patients receiving an anthracycline-based regimen, pertuzumab and trastuzumab are given after completion of the entire anthracycline regimen. INDICATIONS AND DURATION: metastatic breast cancer — give with trastuzumab and docetaxel; pertuzumab and trastuzumab may continue until disease progression or unmanageable toxicity even if docetaxel is stopped. Early breast cancer, neoadjuvant — 3 to 6 cycles with trastuzumab and chemotherapy. Early breast cancer, adjuvant — with trastuzumab for a total of one year (up to 18 cycles, or until disease recurrence or unmanageable toxicity, whichever occurs first), starting on Day 1 of the first taxane-containing cycle and continuing even if chemotherapy is discontinued. DELAYED OR MISSED DOSES: if less than 6 weeks between sequential infusions, give the 420 mg dose as soon as possible then revert to the original schedule; if 6 weeks or more, re-administer the 840 mg loading dose over 60 minutes followed by 420 mg every 3 weeks. DOSE MODIFICATION: dose reductions are not recommended for pertuzumab or trastuzumab; if trastuzumab is discontinued, pertuzumab should also be discontinued. LEFT VENTRICULAR DYSFUNCTION: withhold both for at least 3 weeks for any signs or symptoms suggestive of congestive heart failure, and discontinue pertuzumab if symptomatic heart failure is confirmed. Metastatic disease — pre-treatment LVEF must be at least 50%; withhold for at least 3 weeks for a drop in LVEF to less than 40%, or LVEF 40-45% with a fall of at least 10 percentage points below pre-treatment value; may resume if LVEF recovers to above 45%, or to 40-45% with a difference of less than 10 percentage points below pre-treatment. Early breast cancer — pre-treatment LVEF must be at least 55% (at least 50% after completion of any anthracycline component); withhold for at least 3 weeks for a drop below 50% with a fall of at least 10 percentage points; may resume if LVEF recovers to at least 50% or to within 10 percentage points of pre-treatment. INFUSION REACTIONS: the infusion rate may be slowed or interrupted for an infusion-related reaction and resumed when symptoms abate; discontinue immediately and permanently for NCI-CTCAE Grade 4 reaction (anaphylaxis), bronchospasm or acute respiratory distress syndrome. ELDERLY: no dose adjustment necessary in patients 65 years and over; limited data above 75 years. HEPATIC IMPAIRMENT: not studied; no specific dose recommendations can be made. PAEDIATRIC: safety and efficacy below 18 years have not been established and there is no relevant use in the paediatric population for breast cancer. SOURCE LIMITS: eMC §4.5 was not fetched and §4.4/§4.8 were truncated; no interaction section is reproduced in this draft.