Eribulin Mesylate Demonstrates Real-World Efficacy in Metastatic Breast Cancer

Author(s):

Eribulin mesylate induced favorable responses and improved survival when used as a third or later line of treatment in patients with metastatic breast cancer, including those with triple-negative breast cancer.

Takashi Owa, PhD

Eribulin mesylate (Halaven) induced favorable responses and improved survival when used as a third or later line of treatment in patients with metastatic breast cancer, including those with triple-negative breast cancer (TNBC), according to 10-year data from a real-world study published in Advances in Therapy.¹

In the overall patient population (n = 513), eribulin elicited an overall response rate (ORR) of 54.4% (95% CI, 50.1-58.7%) and a clinical benefit rate (CBR) of 52.3% (95% CI, 52.4-61.0%). The median progression-free survival (PFS) in this subset was 6.1 months (95% CI, 5.8-6.6), while the median overall survival (OS) was 10.6 months (95% CI 9.9-11.7).

In the subgroup of patients with TNBC (n = 256), the agent induced an ORR of 55.1% (95% CI, 48.8-61.2%) with a CBR of 57.4% (95% CI, 51.1-63.5%). The median PFS and OS was 5.8 months (95% CI, 5.1-6.4) and 9.8 months (95% CI, 8.6-11.0), respectively.

"For oncologists and people living with metastatic breast cancer, these data provide insights into [eribulin in] real-world practice," Dr. Takashi Owa, vice president, chief medicine creation officer, and chief discovery officer of Oncology Business Group at Eisai, stated in a press release.² "We have remained committed to the continued data generation for [eribulin], both in the real-world setting and in translational research related to metastatic breast cancer, to drive our continued innovation for difficult-to-treat diseases like metastatic breast cancer."

Eribulin mesylate is a novel nontaxane inhibitor of microtubule dynamics that was approved by the FDA in November 2010 for use in patients with metastatic breast cancer who had undergone 2 prior chemotherapy regimens for metastatic disease; this included an anthracycline and a taxane in the adjuvant or metastatic setting.³ The decision was was based on data from the phase 3 EMBRACE study (NCT00388726), in which the agent demonstrated an OS benefit of 2.5 months vs physician's choice in patients with metastatic disease who had previously been treated with 2 to 5 prior lines of therapy.⁴

In the years following the approval of eribulin, the effectiveness of the agent in real-world clinical practice has been shown in prospective observational studies and retrospective analyses done in several populations and treatment settings on a global scale. However, most of these studies have been performed outside of the United States. The treatment for metastatic breast cancer has evolved in the decade since the approval of eribulin. In light of these advances, the investigators set out to evaluate the real-world efficacy of eribulin in a diverse cohort of patients with metastatic breast cancer, including TNBC.

To this end, a retrospective, multisite patient chart review was done. Physicians who were invited to contribute to the study had been recruited from the Cardinal Health Oncology Provider Extended Network. Those who participated in the study filled out an initial feasibility request that stated they treated more than 2 patients with metastatic breast cancer per month who satisifed the eligibility criteria. Physicians performed the data abstraction themselves, and all abstracted data were been deidentified.

The study was limited to female patients aged at least 18 years of age at the time of eribulin initiation. Additionally, patients needed to have received at least 2 chemotherapy regimens in the metastatic setting before eribulin. All had received an anthracycline and a taxane either in the adjuvant or metastatic setting. Those who were treated with eribulin for indications beyond metastatic breast cancer were excluded from the analysis.

A total of 513 electronic case report forms were included in the analysis and data were abstracted by 46 physicians. In the overall patient population, the median age was 59.0 years (range, 26-86), and 32.9% were aged 65 years or older. The majority of patients were Caucasian (64.9%) and non-Hispanic (89.5%), while 26.3% were African American. Notably, patient demographics within the TNBC cohort were comparable to those in the overall patient population.

Eribulin was most frequently utilized in the third-line setting (78.0%), with the remaining patients receiving the agent in the fourth to seventh line. At the initiation of treatment, most patients (61.0%) had an ECOG performance status of 0 or 1. Moreover, 45.4% of patients had hormone receptor–positive and HER2-negative disease, while 49.9% had TNBC.

Similarly, most patients within the TNBC cohort received eribulin as a third-line treatment (87.9%), and two-thirds of patients had an ECOG performance status of 0 or 1. Over 90% of patients had visceral metastatic disease at the time of drug initiation, with the most common metastatic sites being the lung (66.7%) and liver (57.3%).

Nearly all patients within the overall patient population and TNBC cohort had discontinued treatment with eribulin by the time of data cut-off, at 96.9% in both cohorts. Among all who discontinued treatment, the median treatment duration of eribulin treatment was 5.5 months (range, 0.03–21.5) in the overall population and 5.4 months (range, 1.2-21.5) in the TNBC subgroup.

The majority of patients discontinued treatment because of disease progression in both the overall group and TNBC group, at 78.1% and 84.3%, respectively. Other reasons for discontinuation included decline in performance status (4.0% and 2.4%, respectively), referral to hospice (5.0% and 6.1%, respectively), palliative care (3.4% and 0.4%, respectively), completion of treatment (4.8% in both), patient choice (2.2% and 1.2%, respectively), and other reasons (1.4% and 0.4%, respectively). Only 1.0% of the overall population and 0.4% of the TNBC cohort discontinued due to toxicity or intolerability.

After treatment discontinuation, 34.1% of all patients (n = 175) and 38.7% of those with TNBC (n = 99) went on to receive another line of therapy; the median time to next treatment was 8.1 months (range, 1.6-22.4) and 8.3 months (range, 2.1-22.4) in the overall and TNBC cohorts, respectively.

Additional data indicated that 8.0% of the overall patient population experienced a complete response (CR; n = 41) to eribulin, while 46.4% (n = 238) had a partial response (PR), 17.2% (n = 88) achieved stable disease, and 28.5% (n = 146) had progressive disease. The time to best response among responders was a median of 3.0 months. The duration of best response among 261 patients who achieved a CR and PR was a median of 4.5 months (range, 2.9-7.1).

Moreover, patients within the TNBC subgroup experienced a CR rate of 5.9% (n = 15) and a PR rate of 49.2% (n = 126). Moreover, 18.0% (n = 46) of patients within the subgroup achieved stable disease and 27.0% (n = 69) experienced progressive disease. Among responders, the time to best response was a median of 2.8 months (range, 2.1-3.9) while the median duration of best response was 4.2 months (range, 2.8-6.6) among 132 patients who achieved a CR and PR.

Additionally, 78.4% (n = 402) of the overall patient population, including 85.5% (n = 219) of the TNBC subgroup, had progressed on eribulin therapy at the time of the data cut-off. Over halfof patients in the overall patient population (51.2%; n = 262) were alive and progression free at 6 months (95% CI, 46.8%-55.5%), while 19.2% (n = 94; 95% CI, 15.8%-22.8%) were alive and progression free at 12 months. Moreover, among those with TNBC, 48.0% (n = 125; 95% CI, 41.8%-54.0%) were alive and progression free at 6 months and 15.4% (n = 38; 95% CI, 11.3%-20.2%) were alive and progression free at 12 months.

Other data indicated that 80.9% (n = 415) of the overall patient population and 86.7% (n = 222) of the TNBC subgroup had died as of the time of the data cut-off. At 12 months, 43.9% (95% CI, 39.6%-48.2%) of the overall patient population were alive, while 23.9% (95% CI, 20.2%-27.7%) were alive at 24 months. Among patients with TNBC, 40.3% (95% CI, 34.3%-46.3%) were alive at 12 months and 17.6% (95% CI, 13.1%-22.6%) were alive at 24 months.

“Our real-world cohort was racially diverse, included patients with poor functional status, and half of the patients had TNBC,” the study authors concluded. “Despite thes patient characteristics, which are generally associated with worse outcomes, results from the current analyses indicate that both response rate and survival with eribulin therapy supports the clinical outcomes observed within the eribulin arm in the pivotal clinical trial.”

References

Mougalian SS, Kish JK, Zhang J, et al. Effectiveness of eribulin in metastatic breast cancer: 10 years of real-world clinical experience in the United States. Adv Ther. 2021;38 (5):2213-2225. doi:10.1007/s12325-020-01613-6
Eisai announces real-world data on the effectiveness of Halaven (Eribulin mesylate) for the treatment of patients with metastatic breast cancer (MBC) published in advances in therapy. News release. Eisai. May 18, 2021. Accessed May 19, 2021. https://bit.ly/3bGfox7
Eribulin mesylate. Package insert. Eisai; 2010. Accessed May 19, 2021. https://bit.ly/3yoDR3R
Cortes J, O'Shaughnessy J, Loesch D, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377(9769):914-923. doi:10.1016/S0140-6736(11)60070-6