Abstract P5-15-11: Eribulin should be a candidate strategy in combination with pertuzumab plus trastuzumab for taxane pretreated HER2 positive advance breast cancer

Abstract

Background: Pertuzumab (P) improves clinical outcome when combined with docetaxel and trastuzumab (T). The efficacy of continuing multiple anti-HER2 therapy including P and/or T after initial progression is unclear. Eribulin mesylate (ERI) is able to overcome taxane (TAX) resistance advanced breast cancer (ABC). The objective of this study is to investigate the efficacy and safety of ERI plus P and T for both TAX and T pretreated HER2-positive ABC. Methods: This is a single institute, open-label, single-arm, Phase II study with pharmacokinetics (PK) of ERI (UMIN000012375). The initial dose of P is 840 mg, followed by 420 mg q3w; the initial dose of T 8 mg/kg, followed by 6 mg/kg q3w; ERI is administered at 1.4 mg on Days 1 and 8 of each cycle, q3w. Dose reductions of ERI (to 1.1 and 0.7 mg/m2) were permitted to manage any toxicity (more than grade 3). Patients (Pts) must have previous treatment with both TAX and T. The primary endpoint is assessed overall response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), safety, and PK of ERI. Left ventricular ejection function (LVEF) was evaluated before and end of this study. Results: Thirty Pts were enrolled. Median age at baseline was 57 years. Half of Pts had endocrine positive. All Pts were treated with TAX and T. Twenty-one Pts were treated with anthracycline-based treatment (70%). Median number of previous chemotherapy was 4 (2-5). Pts had multiple metastases, 40% with bone, 36.7% with lung, 20% with liver, and 10% with brain. Pts received a median number of 8 cycles of ERI (mean dose 1.2 ± 0.19 mg/sqm), 8 cycles of both P and T. Total number of 27 Pts needed to reduce dose of ERI because of adverse events (AEs) especially grade 3 neutropenia. The ORR (CR+PR) was 34.8% (95% CI 16.4-57.3, n=23) with median PFS of 42.6 weeks (95% CI 20.3-51.9, n=30). Clinical benefit rate (CR+PR+≥6 month SD) was 60.9% (95% CI 16.4-57.3%). T-DM1 pretreated affected poor outcome than the other factors (p=0.0011). The most common grade 3/4 AEs were neutropenia in 20 Pts (66.7%) without febrile neutropenia. Grade 1/2 AEs were fatigue in 24 Pts (80%), anorexia in 23 Pts (76.7%), anemia in 22 Pts (73.3%), diarrhea in 20 Pts (66.7%), peripheral neuropathy in 16 Pts (53.3%), and hand-foot syndrome in 12 Pts (43.3%). Baseline LVEF was 67%. One Pt had asymptomatic LVEF decrease (below an absolute value of 55%). Otherwise, there was no overall decrease in mean LVEF from baseline. Nine points (pre-dose, end of infusion, 0.5, 1, 2, 4, 24, 72, and 168 h after ERI) of PK analyses were evaluated in 6 Pts, and 3 point (pre-dose, end of infusion, and 168 h after ERI) in 10 Pts. PK parameters of ERI were as follows; Maximum plasma concentration (Cmax) was 375.96 (257.6-531.8) ng/ml, terminal half-life was 36.807 (31.90-40.80) h, total clearance was 1.945 (1.15-3.15) L/h/m2. Cmax of ERI was not correlated with neutrophil count (R2=0.2338, n=16). Conclusions: The combination of ERI plus P and T was well tolerated; no new safety signals ware observed. PK parameter of ERI were as same as previous reports when combined with both P and T. ERI might be a one of strategy in combination with P plus T for TAX pretreated HER2 positive ABC. Citation Format: Araki K, Fukada I, Kobayashi K, Takahashi S, Ito Y. Eribulin should be a candidate strategy in combination with pertuzumab plus trastuzumab for taxane pretreated HER2 positive advance breast cancer [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 P5-15-11.

Perspectives on The Mechanism of Action and Clinical Application of Eribulin for Metastatic Breast Cancer

“…Similarly, another Phase II trial showed that first-line eribulin/trastuzumab treatment in patients with HER2-positive MBC resulted in antitumor activity and was well-tolerated, regardless of prior (neo)adjuvant trastuzumab treatment [50]. A Phase II trial of eribulin in combination with trastuzumab and pertuzumab showed that the combination was well-tolerated and may represent a treatment strategy for taxane-pretreated, HER2-positive, advanced breast cancer [51].…”

Resolution of the Advisory board “Prospects for study and use of eribulin in advanced breast cancer”

“…При этом ВБП коррелировала с пред-шествующей терапией TDM-1, и при ее отсутствии ме-диана ВБП составила 45,6 недель. Профиль безопасно-сти данной комбинации был приемлемым и сопоставим с известными профилями эрибулина, трастузумаба и пертузумаба [13].…”

“…Час тота объективного ответа при использовании данной комбинации в первой линии терапии состави-ла 41,2 % и ЧКЭ -47,1 %. При этом степень экспрессии PD-L1 не являлась прогностическим фактором эффек-тивности, а переносимость данного режима была при-емлемой [13]. Данная комбинация находится в процессе дальнейшего изучения, результаты будут представлять-ся на международных конгрессах.…”