Abstract PS10-24: Infusion related reactions in the phase 3 SOPHIA trial of margetuximab + chemotherapy vs trastuzumab + chemotherapy in patients with pretreated HER2+ metastatic breast cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2021-02, Vol.81 (4_Supplement), p.PS10-24-PS10-24
• Main Authors: Cortes, Javier, Cardoso, Fatima, Curigliano, Giuseppe, Gradishar, William J, Im, Seock-Ah, Rugo, Hope S, Bahadur, Shakeela W, Falcone, Alfredo, Murillo, Serafin Morales, Riseberg, David A, Musolino, Antonino, Feinstein, Trevor M, Abreu, Miguel H, Im, Young-Hyuck, Novik, Yelena, Pluard, Timothy, Salazar, Lupe G, Berardi, Rossana, Pop, Viorela, Hong, Shengyan, Jacobs, Kenneth, Rock, Edwin, Pegram, Mark D
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.SABCS20-PS10-24

Background: Margetuximab (M) is an investigational Fc-engineered, anti-HER2 monoclonal antibody with the same epitope specificity as trastuzumab (T). Relative to T, Fc engineering of M increases binding affinity for the activating Fc receptor (FcR) CD16A and decreases affinity for the inhibitory FcR CD32B. The SOPHIA trial (NCT02492711) randomized pretreated HER2+ MBC patients to either M or T, each with chemotherapy (C). M+C improved progression-free survival (PFS) benefit over T+C. Infusion related reactions (IRR) have been observed after infusion of therapeutic proteins, typically during the first infusion, with a first-dose incidence of up to 40% for T (Herceptin Prescribing Information®). A retrospective analysis of 197 patients showed 16% IRRs on T, mostly after the first infusion; this rate was lower with (10%) compared to without (19%) premedication (Thompson, 2014). Here, we report IRR safety and tolerability data in the SOPHIA trial patients following HER2-targeted antibody therapy. Methods: The open-label Phase 3 SOPHIA trial enrolled patients with HER2+ MBC after at least 2 prior anti-HER2 therapies, including pertuzumab; 91% in both groups also received ado-trastuzumab emtansine. Randomization of 536 patients was 1:1 to M (15 mg/kg IV q3w) or T (6 [8 loading dose] mg/kg IV q3w), each with Investigator selected C (standard dose capecitabine, eribulin, gemcitabine, or vinorelbine). M was given as 120-minute infusions. T was given as a 90-minute infusion in Cycle 1, then a 30-minute infusion from Cycle 2 onward. Recommended elective premedication included acetaminophen, ibuprofen, diphenhydramine, ranitidine, dexamethasone, or equivalents. IRR safety analyses were conducted on 530 patients (264 M+C and 266 T+C) that received any study therapy. Results: A higher proportion of patients experienced IRRs on the M arm (35 [13.3%]) than on the T arm (9 [3.4%]). Most IRRs in both groups were severity Grade 1 or 2, occurred on Cycle 1 Day 1, and resolved within 24 hours. In patients receiving M, Grade 3 IRR occurred in 4 patients (1.5%), including 3 after vinorelbine and 1 after eribulin. Adverse events associated with Grade 3 IRRs included chills, fever, nausea, diarrhea, dyspnea, and/or hypertension. Two patients receiving M (0.8%) discontinued due to IRR, versus none on T. Of patients with IRRs, the most common symptoms in both treatment groups were chills (M: 17 [48.6%]; T: 5 [55.6%]) and fever (M: 13 [37.1%]; T: 2 [22.2%]). There was no observed hyp