Subcutaneous trastuzumab (H SC) with intravenous pertuzumab (P IV) and docetaxel (D IV) in HER2-positive advanced breast cancer (BC): MetaPHER second interim analysis

Abstract

Background: HSC (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 interimsafety and preliminary efficacy. Methods: Pts are≤18-year-old females whose disease was not previously treated with systemic non-hormonal anticancer therapy. Pts receive 600 mg fixed-doseH 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. Results: 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 toH SC only). No MedDRApreferred- termcongestive 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). Conclusions: 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 theH IV + P IV combination, and no new safety signals identified. The final analysis is planned for 2019.