|Pharmacotherapeutic group: Other antineoplastic agents, ATC code: L01XX41HALAVEN (eribulin mesilate) is a non-taxane, microtubule dynamics inhibitor belonging to the halichondrin class of antineoplastic agents. It is a structurally simplified synthetic analogue of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai.Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into non-productive aggregates. Eribulin exerts its effects via a tubulin-based antimitotic mechanism leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. |
Clinical efficacyThe efficacy of HALAVEN in breast cancer is supported by two single-arm Phase 2 studies and a randomized Phase 3 comparative study. The 762 patients in the pivotal Phase 3 EMBRACE study had locally recurrent or metastatic breast cancer, and had previously received at least two and a maximum of five chemotherapy regimens, including an anthracycline and a taxane (unless contraindicated). Patients must have progressed within 6 months of their last chemotherapeutic regimen. They were randomized 2:1 to receive either HALAVEN at a dose of 1.23 mg/m2 on Days 1 and 8 in a 21‑day cycle administered intravenously over 2 to 5 minutes, or treatment of physician's choice (TPC), defined as any single-agent chemotherapy, hormonal treatment, or biologic therapy approved for the treatment of cancer; or palliative treatment or radiotherapy, reflecting local practice. The TPC arm consisted of 97% chemotherapy (26% vinorelbine, 18% gemcitabine, 18% capecitabine, 16% taxane, 9% anthracycline, 10% other chemotherapy), or 3% hormonal therapy.The study met its primary endpoint with an overall survival result that was statistically significantly better in the eribulin group compared to TPC at 55% of events. The median survival of the HALAVEN group (median: 399 days/13.1 months) compared with the TPC group (median: 324 days/10.6 months) improved by 75 days/2.5 months (HR 0.809, 95% CI: 0.660, 0.991, p=0.041).This result was confirmed with an updated overall survival analysis carried out at 77% of events with the median survival of the HALAVEN group (median: 403 days/13.2 months) compared with the TPC group (median: 321 days/10.5 months) improved by 82 days/2.7 months (HR 0.805, 95% CI: 0.677, 0.958, nominal p=0.014).
Efficacy of HALAVEN versus Treatment of Physician's Choice Updated Survival Analysis in the ITT Population
a Stratified by geographic region, HER2/neu status, and prior capecitabine therapy.
(n = 508)
(n = 254)
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Number of Events
Hazard Ratio (95% CI)a
(Cox proportional hazards)
Kaplan-Meier Analysis of OS-Update Data (ITT Population)At the time of the original cut-off, analysis of progression free survival by independent and investigator review is shown in the following table.
Efficacy of HALAVEN versus Treatment of Physician's Choice Progression Free Survival
In response evaluable patients who received HALAVEN, the objective response rate by the RECIST criteria was 12.2% (95% CI: 9.4%, 15.5%) by independent review and 13.2% (95% CI: 10.3%, 16.7%) by investigator review. The median response duration in this population by independent review was 128 days (95% CI: 116, 152 days) (4.2 months).The positive effect on OS and PFS was seen in both taxane-refractory and non-refractory groups of patients. In the OS update, the HR for eribulin versus TPC was 0.90 (95% CI 0.71, 1.14) in favour of eribulin for taxane-refractory patients and 0.73 (95% CI 0.56, 0.96) for patients not taxane-refractory. In the Investigator assessment-based analysis of PFS (based on original data cut-off), the HR was 0.77 (95% CI 0.61, 0.97) for taxane-refractory patients and 0.76 (95% CI 0.58, 0.99) for patients not taxane-refractory.The positive effect on OS was seen both in capecitabine-naïve and in capecitabine pre-treated patient groups. The analysis of updated OS showed a survival benefit for the eribulin group compared to TPC both in capecitabine pre-treated patients with a HR of 0.787 (95% CI 0.645, 0.961), and for the capecitabine-naïve patients with a corresponding HR of 0.865 (95% CI 0.606, 1.233). Investigator assessment-based analysis of PFS (based on original data cut-off), also showed a positive effect in the capecitabine pre-treated group with a HR of 0.68 (0.56, 0.83). For the capecitabine-naïve group the corresponding HR was 1.03 (0.73, 1.45).
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Number of events
(101 ‑ 118)
0.865 (0.714 1.048)
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Number of events
(100 ‑ 114)
0.757 (0.638 0.900)
For the hazard ratio, a value less than 1.00 favours eribulin
Stratified by geographic region, HER2/neu status, and prior capecitabine use.
Paediatric populationThe European Medicines Agency has waived the obligation to submit the results of studies with eribulin in all subsets of the paediatric population in the indication of breast cancer.