Eribulin in combination with pertuzumab plus trastuzumab for HER2-positive advanced or recurrent breast cancer (JBCRG-M03).

Abstract

1025 Background: Pertuzumab (P) provided overall and progression-free survival (PFS) benefits in HER2-positive metastatic breast cancer (MBC) in the CLEOPATRA study as a first-line therapy. However, long-term administration of intravenous docetaxel at a dose of 75 mg/m2 every 3 weeks in MBC patients is difficult. Eribulin (E) is a well-tolerated cytotoxic agent. We report the efficacy and safety of E in combination with trastuzumab (T) plus P as first- and second-line therapy for metastatic or advanced BC in a multicenter, open-label phase II study (UMIN000012232). Methods: HER2-positive advanced or recurrent BC patients with no or a single prior therapy as advanced or recurrent chemotherapy were enrolled. All patients were administered T and taxane as adjuvant or first-line chemotherapy. Treatment consisted of E 1.4 mg/m2 on days 1 and 8 of a 21-day cycle and T (8 mg/kg loading dose > 6 mg/kg) plus P (840 mg loading dose > 420 mg) once every 3 weeks, all given intravenously. The primary end point was PFS. Results: From November 2013 to April 2016, 50 patients were enrolled. Forty-nine patients were eligible for safety analysis; full analysis set (FAS) includes 46 patients. The median patient age was 56 years (range 23–70), and 8 (16%) and 41 (84%) patients were treated in first- and second-line settings, respectively. Twenty-eight patients out of 49 patients (57%) continued the protocol therapy at the end of 8 cycles and median PFS was not yet reached. The response rate by RECIST ver.1.1 was 56.5% in FAS. The relative dose intensity of E, T, and P were 93.3% (range 77.0%–100%), 100% (range 96.0%–100%) and 100% (range 89.7%–100%), respectively in FAS. The grade 3/4 adverse effects (AE) were neutropenia in 5 patients (10.2%) including 2 patients (4.1%) with febrile neutropenia, hypertension in 3 patients (6.1%), and other AEs in only one patient. Average of the ejection fraction did not decrease significantly. Symptomatic left ventricular systolic dysfunction was not observed. Conclusions: E in combination with T plus P was well-tolerated and could be an alternative to docetaxel-based combination therapy for HER2-positive MBC. Clinical trial information: 000012232.