Eribulin mesylate (Halaven) proved safe and effective as first-line therapy for locally recurrent or metastatic HER2-negative breast cancer in final phase II clinical trial results
Kristi J. McIntyre, MD
Eribulin mesylate (Halaven) proved safe and effective as first-line therapy for locally recurrent or metastatic HER2-negative breast cancer in final phase II clinical trial results presented at the 2013 San Antonio Breast Cancer Symposium, laying the groundwork for moving the drug forward in the treatment timeline.1
The objective response rate (ORR), the study’s primary endpoint, was 28.6% among the 56 patients treated during the single-arm, open-label trial. The clinical benefit rate, a secondary endpoint that includes partial and complete responses and stable disease ≥6 months, was 51.8%. The median progression- free survival was 6.8 months. The adverse events (AEs) were consistent with the established safety profile of the drug, the researchers noted.
“Eribulin compared quite favorably to other firstline agents for metastatic breast cancer,” said lead investigator Kristi J. McIntyre, MD, a medical oncologist at Texas Oncology-Dallas Presbyterian Hospital, a practice in The US Oncology Network, during an interview at SABCS. “Our population had never had any treatment for metastatic breast cancer.”
Plans are under way for a phase III trial comparing eribulin with standard weekly paclitaxel as first- or second-line therapy, according to the NIH Clinical Trials Registry.2 Eisai Inc, which is sponsoring the trial, is seeking to recruit 910 patients with HER2-negative locally recurrent or metastatic breast cancer.
Joyce A. O’Shaughnessy, MD
Joyce A. O’Shaughnessy, MD, who has conducted extensive research into eribulin and participated in the phase II study, said in an interview that eribulin warrants exploration in first-line neoadjuvant and adjuvant settings.
“Eribulin really is one of our best drugs for metastatic breast cancer for the simple reason it is one of the few things that has a high level of evidence for non-crossresistance,” said O’Shaughnessy, co-Director of Breast Cancer Research at Baylor Charles A. Sammons Cancer Center, Texas Oncology, a practice in The US Oncology Network in Dallas. “We don’t have that many things that we can reliably give to patients to which they will respond more often than not.”
Saying that eribulin had demonstrated a clear survival benefit, the FDA approved the drug in 2010 for the treatment of patients with metastatic disease who have received at least two chemotherapeutic regimens in a metastatic setting. The indication specifies that an anthracycline and a taxane should be part of prior adjuvant or metastatic therapy.
Synthetically developed from a marine sponge, eribulin is a nontaxane microtubule inhibitor with a novel mechanism of action that differs from other drugs in the same class. “It inhibits microtubules in a dynamic fashion and in a different site than the other taxanes do, ” said McIntyre. “Clinically, its being a nontaxane is important because you don’t have hypersensitivity reactions and the requirements for premedications.”
She also said it offers ease of administration and convenience for patients.
CBR (CR + PR + SD)
Median months, (range) 95% CI
CBR indicates clinical benefit rate; CR, complete response; DOR, duration of response; ORR, objective response rate; PFS, progression-free survival; PR, partial response; SD, stable disease ≥6 months; TTR, time to first response
The participants in the trial were a median age of 57 years (range, 31-85 years); all patients were diagnosed with stage IV disease and nearly 70% had visceral metastases. Although all patients were HER2-negative, 78.6% were either estrogen or progesterone receptor- positive while the remainder of participants had triple-negative disease. The drug conferred benefit regardless of hormone status, but the patient pool was too small for subset analysis, McIntyre said.
Nearly half of the patients had received anthracycline- based therapy in any setting, while 44.6% had been given taxanes as neoadjuvant or adjuvant therapy. Eribulin was administered at 1.4 mg/m2 IV on days 1 and 8 of each 3-week cycle for 2 to 5 minutes. In all, 57% of participants in the trial completed at least 6 cycles of therapy, and most of the patients who did not reach that milestone halted treatment due to progressive disease.
The most frequently reported treatment-related AEs (all occurring in >50% of patients) were alopecia, neutropenia, fatigue, and peripheral neuropathy, with serious AEs affecting 5 patients (8.9%). Four patients experienced grade 3/4 febrile neutropenia. Of the 6 patients who discontinued therapy, 5 did so because of peripheral neuropathy, according to the poster presentation.
McIntyre said investigators “will be looking quite closely at the peripheral neuropathy rate” as the larger clinical study is conducted. She said prior clinical trial evidence indicates that those patients who developed peripheral neuropathy had been treated with taxanes, meaning “there was prior microtubule treatment.”