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

Aim: To characterise risk of anaphylaxis/hypersensitivity with intravenous pertu-zumab 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.Methods: A 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. Results: This analysis includes 4772 patients who received PH IV and/or PH FDC SC. Inci-dence 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 dis-continuations 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).Conclusion: PH IV and PH FDC SC were well tolerated, with few grade >3 anaphylaxis/hy-persensitivity events reported with PH IV and no grade >3 related events with PH FDC SC. Most events occurred during chemotherapy.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).