H SC (Herceptin® SC) was approved based on the HannaH study (Ismael Lancet Oncol 2012). The single-arm, open-label MetaPHER study (NCT02402712) is the first large Phase IIIb study to evaluate the safety and tolerability of H SC + P IV (PERJETA®) + D IV as first-line treatment in patients (pts) with HER2-positive metastatic/locally advanced BC. Here, we report interim safety and preliminary efficacy.
Pts are ≥18-year-old females whose disease was not previously treated with systemic non-hormonal anticancer therapy. Pts receive 600 mg fixed-dose H SC q3w + 840 mg loading/420 mg maintenance P IV q3w + ≥6 cycles D IV q3w (>6 at investigator’s discretion; 75 mg/m2 initial dose) until disease progression (PD), unacceptable toxicity, withdrawal of consent, death or predefined study end. The primary endpoint is overall and cardiac safety and tolerability. Adverse events (AEs) are graded per NCI–CTCAE v4.0.
Of 418 enrolled pts, 412 started study treatment; 330 (196 on treatment, 134 in follow-up [FU]) were on study by data cutoff (5 Jan 18). Median FU duration was 16.3 months. In the safety population 406/412 pts (98.5%) experienced ≥1 any-grade AE; 213 (51.7%) grade ≥3 AEs; 101 (24.5%) serious AEs (SAEs); and 86 (20.9%) AEs leading to P IV, H SC or D IV discontinuation. 47 pts (11.4%) died: 38 (9.2%) due to PD; 9 (2.2%) due to AEs; none from cardiac death. AEs of interest included grade ≥3 cardiac AEs (3 pts; 0.7%); ejection fraction decrease to < 50% and ≥10% points from baseline (32; 7.8%); investigator-reported administration-related and local injection-site reactions (80; 19.4%, including 19 [4.6%] with an AE related to H SC only). No MedDRA-preferred-term congestive heart failure was reported. 249/336 pts with baseline measurable disease had an objective response (74.1% [95% CI 69.1–78.7]). The clinical benefit rate was 81.1% (334/412 pts [95% CI 77.3–84.9]). 1-year progression-free survival was 63.1% (95% CI 58.4–68.2).
Safety and efficacy profiles of H SC + P IV as first-line treatment for pts with HER2-positive advanced BC were consistent with the known profiles for the H IV + P IV combination, and no new safety signals identified. The final analysis is planned for 2019.
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
Support for third-party writing assistance for this abstract, furnished by Helen Keyworth, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.
S. Kümmel: Honoraria: Roche, Celgene, Novartis, Amgen and Daiichi Sankyo; Consultant/advisor: Roche; Travel/accommodations/expenses: Roche and Celgene. C.A. Tondini: Consultant/advisor: Myriad Genetics; Speakers’ bureau: Amgen; Travel/accommodations/expenses: Roche/Genentech, Novartis and Celgene. J. Abraham: Honoraria, including travel expenses for advisory roles: Novartis and Genomic Health. Z.I. Nowecki: Travel/accommodations/expenses: Roche/Genentech, Novartis and Amgen. A. Juarez: Honoraria, support for national and international congresses and clinical trials: Roche. F. Morales-Vásquez: Honoraria, educational grants and Speakers’ bureaus: Roche, AstraZeneca, Pfizer, MSD, Novartis, Teva and Eli Lilly. S. Cardona-Huerta: Honoraria for advisory and consulting/speaker roles: Roche. D. Heinzmann: Employee: F. Hoffmann-La Roche; Shares: Roche. J. He: Employee: F. Hoffmann-La Roche. A.N. Duc, A. Crepelle-Fléchais: Employee: F. Hoffmann-La Roche. M. Martín: Honoraria: Roche, Genentech, Novartis, Lilly and AstraZeneca; Research grants: Roche and Novartis. All other authors have declared no conflicts of interest.