Incidence and severity of anaphylaxis and hypersensitivity in trials of intravenous pertuzumab plus trastuzumab or the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection for HER2-positive breast cancer

Abstract

AimTo characterise risk of anaphylaxis/hypersensitivity with intravenous pertuzumab plus trastuzumab (PH IV), the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) or concomitant chemotherapy to support potential administration of PH FDC SC by healthcare professionals outside clinics. MethodsA cumulative search for anaphylaxis/hypersensitivity (Roche Standard Adverse Event Group Terms) was performed for all pivotal trials cited in the current EMA P IV/PH FDC SC summaries of product characteristics: MBC: NCT00567190, NCT02402712; EBC: NCT01358877, NCT00545688, NCT00976989, NCT02132949, NCT03493854 and NCT03674112. Occurrence, incidence and severity of events were analysed and a time–trend analysis (by cycle) was performed. ResultsThis analysis includes 4772 patients who received PH IV and/or PH FDC SC. Incidence of all-grade (grade ≥3) anaphylaxis/hypersensitivity events: 3–11% (≤2%) for PH IV MBC trials; 1–13% (0–3%) for PH IV EBC trials; and 2–3% (<1%; not related to PH FDC SC) for PH FDC SC EBC trials. Discontinuations due to anaphylaxis/hypersensitivity were rare for PH IV (generally <1% except two arms of TRYPHAENA: 1% and 3%); no discontinuations of PH FDC SC have been recorded so far. Time–trend analysis showed that most events were reported during the first 6–8 cycles with concurrent chemotherapy, with a decrease in later cycles (except MetaPHER). ConclusionPH IV and PH FDC SC were well tolerated, with few grade ≥3 anaphylaxis/hypersensitivity events reported with PH IV and no grade ≥3 related events with PH FDC SC. Most events occurred during chemotherapy.