Abstract P4-21-42: MetaPHER phase IIIb multicenter, open-label, single-arm safety study of subcutaneous trastuzumab in combination with pertuzumab and docetaxel in patients with HER2-positive advanced breast cancer: First results
Authors: Kümmel S , Abraham J , Martin M , Crepelle-Fléchais A , Swat A , Nüesch E , Shing M , Tondini CA 
Published: March 2017

Abstract
Background: MetaPHER investigates fixed-dose subcutaneous trastuzumab (Herceptin® [H SC]) in combination with intravenous (IV) pertuzumab (PERJETA® [P IV]) plus docetaxel (D IV). The MetaPHER study treatment regimen is based on CLEOPATRA (phase III; NCT00567190), which demonstrated a significant progression-free and overall survival benefit in patients (pts) with HER2-positive metastatic breast cancer (BC) following first-line treatment with IV trastuzumab (Herceptin® [H IV]) plus P IV plus D IV. Fixed-dose H SC was non-inferior to H IV in terms of pathological complete response and serum trough concentration, and had a comparable safety profile to H IV, in pts with HER2-positive early BC in HannaH (phase III; NCT00950300). Furthermore, PrefHer (NCT01401166) results showed compelling patient preference for H SC vs H IV (88.9% vs 9.6%) in the HER2-positive early BC setting. To date, limited data exist for H SC in combination with P IV and D IV; we report the first results of safety and tolerability from MetaPHER for this combination in pts with HER2-positive advanced BC.
Methods: MetaPHER enrollment is ongoing at &gt;100 sites in 12 countries. Females aged ≥18 years with metastatic or locally recurrent HER2-positive BC previously untreated with non-hormonal anticancer therapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, and left ventricular ejection fraction (LVEF) ≥50% receive fixed-dose H SC 600 mg/5 mL q3w, P IV (840 mg loading dose, then 420 mg at subsequent cycles q3w), and D IV (at least 6 cycles with a recommended initial dose of 75 mg/m2 q3w; possible escalation to 100 mg/m2 q3w and continuation of D IV after Cycle 6 at the investigator's discretion). Study treatment is given until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end, whichever occurs first. The primary endpoint is safety and tolerability of H SC in combination with P IV and D IV in pts with HER2-positive advanced BC. Adverse events (AEs) and serious AEs (SAEs) were graded per National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Results are descriptive.
Results: 150 pts were enrolled and received a median of 4 treatment cycles by the data cutoff date of June 23, 2016. Safety data are shown in the table.
Pts with ≥1 event, n (%)H SC + P IV + D IV (N = 150)Any grade AEs136 (90.7)Grade ≥3 AEs59 (39.3)SAEs23 (15.3)Deaths2 (1.3)AEs leading to discontinuation of H SC, P IV, or D IV16 (10.7)AEs leading to discontinuation of H SC5 (3.3)AEs of Interest Administration-related and local injection-site reactions for H SC5 (3.3)*Cardiac: Grade ≥3 cardiac AEs†1 (0.7)Any grade congestive heart failure‡0Pts with a significant LVEF drop§1 (0.7)*Grade 1 & 2 AEs only; †Events classified as System Organ Class Cardiac Disorders; ‡Preferred terms of reported AEs; §≥10% from baseline to LVEF &lt;50%.
Conclusion: MetaPHER's first report of H SC with P IV and D IV as first-line treatment for pts with HER2-positive advanced BC is consistent with the known safety profile for H IV with P IV and D IV from CLEOPATRA, and no new safety signals were identified.

Citation Format: Kümmel S, Abraham J, Martin M, Crepelle-Fléchais A, Swat A, Nüesch E, Shing M, Tondini CA. MetaPHER phase IIIb multicenter, open-label, single-arm safety study of subcutaneous trastuzumab in combination with pertuzumab and docetaxel in patients with HER2-positive advanced breast cancer: First results [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-42.