Abstract P1-13-06: Safety of trastuzumab in the subcutaneous formulation for the treatment of HER2 positive early breast cancer (eBC) patients: Primary results of SCHEARLY trial
Authors: Zambetti M , Montemurro F , Morandi P , Zamagni C , Stell A , Rozzi A , Gianni L 
Published: February 2018

Abstract
Background:: This study in Italian breast cancer patients is part of a phase IIIB, open-label, multinational umbrella study (UmbHER1), assessing the safety and tolerability of the subcutaneous (SC) formulation of Trastuzumab as primary end point. Present analysis is relative to the safety during the treatment period, with a major focus to side effects associated with the Trastuzumab SC administration.
Methods: Patients with HER2-positive eBC and LABC were eligible and included in two sequential cohorts: 120 patients treated with Trastuzumab SC by handheld syringe (Cohort A), and 120 with Trastuzumab SC by single-use injection device (SID, Cohort B). All the patients received adjuvant or neo-adjuvant treatment (clinician choice) with Anthracycline-containing regimens (FEC/EC/AC) followed by Trastuzumab SC in combination with taxanes (weekly Paclitaxel or Docetaxel) and then in monotherapy for a total of 18 cycles. Safety clinical and instrumental evaluations were planned at definite time points.
Results: 240 patients were enrolled and 202 patients (82.6% in cohort A and 84.9% in cohort B) completed the treatment. Reasons for discontinuation were the following: 7.9% AE/intercurrent illness, 3.3% withdrew consent, 1.7% recurrence of disease, 1.7% refused treatment, 0.9% violation of inclusion criteria, 0.9% other reasons. In the safety population, 98.2% of patients experienced at least one adverse event from the start of the Anthracycline treatment until the Safety Follow-up visit. Patients experiencing a Treatment Emergent (from Trastuzumab start date) AEs defined as Grade ≥3 were 26.8%; of these, 3.9% were considered related to study drug; Treatment Emergent Serious Adverse Events appeared in 7.5% of the safety population, of which 0.9% were considered related to study drug: one pleuropericarditis and one anaphylactic shock, both resolved.
The frequency of systemic administration-related reactions, ARRs (pyrexia 25%, erythema 20,2%, rash 7,0%, chest pain 7,0%, pruritus 6,6%, chills 1,3%, anaphylactic shock 0,9%) and local injection site reactions, ISRs (pain 6,6%, injection site reactions 3,9%, subcutaneous abscess 0,9%, administration site oedema 0,4%) potentially related to the subcutaneous formulation is cumulatively reported below.
% all / G≥3% related to IMP% related cohort A% related cohort B% during Tax+Trast all/ G≥3% during Trast only all/ G≥3Systemic ARRs68,0 / 2,28,85,33,916.7 / 0.425.0 / 0.4Local ISRs21,9 / 0,97,04,81,36.6 / 0.43.1 / 0.0
The mean reduction of Left Ventricular Ejection Fraction (LVEF) at the end of 1 year treatment from screening was 2.9%. 8.8% of patients experienced a decrease in LVEF, in most cases defined related to study drug (18 patients out of 20); no cases of CHF were reported.
Conclusion: Local and systemic tolerability of subcutaneous Trastuzumab administration is good in both groups and there is no evidence of increased incidence and severity of IMP-related systemic side effects in comparison with the standard intravenous route.
Citation Format: Zambetti M, Montemurro F, Morandi P, Zamagni C, Stell A, Rozzi A, Gianni L. Safety of trastuzumab in the subcutaneous formulation for the treatment of HER2 positive early breast cancer (eBC) patients: Primary results of SCHEARLY trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-13-06.