Abstract P1-18-05: Subcutaneous trastuzumab and hyaluronidase-oysk with intravenous pertuzumab and docetaxel in HER2-positive advanced breast cancer: Final analysis of the phase IIIb, multicenter, open-label, single-arm MetaPHER study
Authors: Kümmel Sherko , Tondini Carlo A , Abraham Jacinta , Nowecki Zbigniew , Itrych Bartosz , Hitre Erika , Karaszewska Bogusława , Juarez Alejandro , Morales-Vásquez Flavia , García Jose Manuel Pérez , Cardona-Huerta Servando , Benyunes Mark , Restuccia Eleonora , Knott Adam , Monturus Estefanía , Sequi Marco , Martín Miguel 
Published: March 2020

Abstract
Background Previous trials showed that fixed-dose subcutaneous trastuzumab and hyaluronidase-oysk (Herceptin Hylecta™; H SC) was non-inferior to weight-based intravenous trastuzumab (Herceptin®; H IV) in terms of pathologic complete response and serum trough concentration in HER2-positive early breast cancer (BC), with a comparable safety profile (NCT00950300), and demonstrated a compelling patient (pt) preference for H SC (NCT01401166). IV pertuzumab (PERJETA®; P IV) + H IV + docetaxel (D IV) was also shown to significantly improve progression-free survival (PFS) and overall survival vs. placebo + H IV + D IV in HER2-positive metastatic BC (NCT00567190). Here we report results from the final analysis of MetaPHER (NCT02402712), the largest study to evaluate safety and tolerability of first-line H SC + P IV + D IV for HER2-positive metastatic/locally advanced BC. Earlier analyses have been reported (Kümmel SABCS 2016; P4-21-42; Kümmel ESMO 2018; 323P). Methods Pts were ≥18-year-old females who had received no previous systemic non-hormonal anticancer therapy for their disease, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and a left ventricular ejection fraction (LVEF) ≥50%. Brain metastases and concomitant hormone therapy were allowed. Pts received 600 mg H SC + 840 mg loading/420 mg maintenance doses of P IV + ≥6 cycles of D IV (75 mg/m2→100 mg/m2; &gt;6 cycles were given at the investigator’s discretion) every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end. The primary objective was to evaluate safety and tolerability. Adverse events (AEs) were graded per National Cancer Institute - Common Terminology Criteria for Adverse Events version 4.0; left ventricular systolic dysfunction (LVSD) was classified according to the New York Heart Association Functional Classification system. Safety results are descriptive. Exploratory efficacy endpoints were PFS and objective response rate (ORR). Results Four hundred eighteen pts were enrolled; 412 were treated and analyzed for safety, and 160 remained on treatment at study end. Data cutoff was May 23, 2019 with median follow-up of 27 months (max. 45 months). Baseline demographics were similar to the interim analysis. Median cycles of H SC, P IV, and D IV were 22.0, 21.5, and 6.0, respectively (some discontinued P IV due to toxicity but remained on H SC per the protocol). Most pts experienced ≥1 any-grade AE (406; 98.5%); 221 (53.6%), grade ≥3 AEs; 107 (26.0%), serious AEs; 87 (21.1%), AEs leading to withdrawal from any study treatment; 87 (21.1%), investigator-reported administration-related and local injection-site reactions (21 [5.1%] H SC-related). There were 87 deaths (21.1% of pts): 73 (17.7%) from disease progression, nine (2.2%) due to AEs, and five (1.2%) due to other causes after treatment discontinuation. Three pts (0.7%) experienced grade ≥3 cardiac AEs, and one (0.2%) a serious AE suggestive of congestive heart failure. Of the 396 pts with LVEF measurements at baseline and ≥1 post-baseline visit, 40 (10.1%) had LVEF drops (to &lt;50% and ≥10% points from baseline; the majority were asymptomatic, grade 1-2, and did not lead to study drug discontinuation); only two (0.5%) had symptomatic LVSD. There were no cardiac deaths. Median investigator-assessed PFS was 18.7 months (234 events [56.8%]). The ORR was 75.6% (95% CI 70.6-80.1; 254/336 pts with measurable disease at baseline); the clinical benefit rate was 92.0% (309 pts). Conclusion The safety profile of first-line H SC + P IV + D IV for HER2-positive advanced BC was consistent with the known safety profile of H IV + P IV + D IV. No new safety signals were identified. Efficacy data were supportive of historical reports of H IV + P IV + D IV.
Citation Format: Sherko Kümmel, Carlo A Tondini, Jacinta Abraham, Zbigniew Nowecki, Bartosz Itrych, Erika Hitre, Bogusława Karaszewska, Alejandro Juarez, Flavia Morales-Vásquez, Jose Manuel Pérez García, Servando Cardona-Huerta, Mark Benyunes, Eleonora Restuccia, Adam Knott, Estefanía Monturus, Marco Sequi, Miguel Martín. Subcutaneous trastuzumab and hyaluronidase-oysk with intravenous pertuzumab and docetaxel in HER2-positive advanced breast cancer: Final analysis of the phase IIIb, multicenter, open-label, single-arm MetaPHER study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-05.