Among patients with HER2-negative stage IIIb/IV breast cancer who have progressed after a taxane or anthracycline therapy, a multicenter single-arm study of third-line eribulin demonstrated both safety and efficacy.
In the first-line setting, recently updated findings from EMBRACE, the phase III trial that led to the 2010 FDA approval of eribulin as monotherapy in patients with relapsed locally advanced or metastatic breast cancer, demonstrated improved survival compared with physician’s choice of controls at 13.2 months versus 10.5 months (HR, 0.81; 95% CI, 0.67-0.96;P= .014) in patients who had received 2 to 5 previous treatment regimens. Eribulin is a fully synthetic macrocyclic analogue of a naturally occurring mitotic inhibitor.
The current study (ONCOSUR 2012-02), which was presented at ESMO, was conducted, as researchers needed data that were specific to third-line treatment for breast cancer, said Sanchez, of University Hospital, Madrid, Spain, in an interview withTargeted Oncology. “We wanted real-world data on these patients,” he added.
ONCOSUR 2012-02 had safety as its primary endpoint, and overall survival (OS), progression-free survival (PFS), clinical benefit rate (CBR), and overall response rate (ORR) as secondary endpoints.
Patients had received 2 prior lines of chemotherapy in the advanced disease setting. Patients received eribulin at 1.23 mg/m2on days 1 and 8 of every 21-day cycle until disease progression, unacceptable toxicity, or withdrawal.
Among 59 patients (mean age 57.7 years), 98.3% had received previous taxanes and/or anthracyclines. Regarding subtypes, 71.2% were estrogen receptor-positive, 66.1% were progesterone receptor-positive, and 20.3% had triple-negative breast cancer. The majority of patients had HER2-negative status (96.6%), and nearly all had metastatic disease (98.3%).
Ductal disease was present in 91.5% of patients. Metastases in the liver were present in 64.4% of patients, 57.6% were in the bone, and 50.9% were in the lung. Nearly half of patients had lymph node metastases (49.2%), and 84.8% had visceral disease. Prior cardiovascular disease was noted in 35.6% of patients. Mean treatment duration was 4.5 months and the mean number of cycles was 6.9.
The most common grade 3/4 adverse event (AE) considered to be associated with eribulin was neutropenia at 16.95%. Other grade 3/4 AEs included febrile neutropenia rate (5.08%), alopecia (5.08%), and leukopenia (5.08%). Grade 1/2 events included asthenia, gamma-glutamyltransferase increase, respiratory tract infection, mucosal inflammation, peripheral neuropathy, and polyneuropathy, all at 1.69%. Dose reductions were required in 52.5% of patients.
The median PFS was 4.03 months (95% CI, 3.07-5.93), while the median OS was 13.6 months (95% CI, 11.8-not reached). “Importantly, this OS rate was very similar to the rate in the phase III trials.” Partial responses were observed in 17.0%, and stable disease in 39.0%, leading to a CBR of 56%. Progression was reported in 35.6% of patients.
At a 20-month follow-up, 44 patients (74.6%) were still alive, Sanchez said. Eleven patients left the study for reasons other than disease progression. Ay the end of the end of the follow-up period (median 2.67 months), 10 (90.9%) had not progressed. Further treatment was administered in 35 (77.8%) of the 45 patients (76.3%) who ultimately had progressive disease.
“Treatment with eribulin as third-line chemotherapy for locally advanced or metastatic breast cancer resulted in minimally toxic, manageable adverse events, similar to the previously described events in the pivotal trials,” Sanchez said. “Treatment was effective with a clinical benefit in more than half of the women treated.”
Additionally, he added that other available regimens for third-line treatment typically have more neuropathy, more hematologic toxicity, and higher rates of alopecia.
“Eribulin is better tolerated. It’s an option for patients with metastatic breast cancer,” he said.
Sanchez LMM, Anton FM, Peron IA, et al. Single arm, multicentre, non-randomized open-label trial to evaluate the safety of eribulin in third line chemotherapy in patients with HER2-negative metastatic or locally advanced breast cancer previously treated with anthracyclines and taxanes: Onsite study (ONCOSUR 2012-02). Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract 246P.