Eribulin mesylate as a microtubule inhibitor for treatment of patients with metastatic breast cancer

Figures & data

Figure 1 Molecular structure of halichondrin B.

Figure 2 Molecular structure of eribulin.

Table 1 Comparison between eribulin and other antimicrotubule agents active in MBC

Compound	Mechanism of action	Efficacy in MBC
Paclitaxel	Enhances polymerization of tubulin and interacts directly with microtubules, stabilizing them against depolymerization	RR, 40%–58% PFS, 9 months OS, 24 months
Docetaxel	Promotes suppression of microtubule dynamics during the assembly and disassembly process	RR, 33% PFS, 5.3 months OS^−
Ixabepilone	Binds to the αβ-tubulin heterodimer subunit and the rate of αβ-tubulin dissociation decreases, and has also been shown to induce tubulin polymerization into microtubules without the presence of GTP	RR, 11.5% PFS, 5.6 months OS, 8.6 months
Vinorelbine	Inhibits mitosis at metaphase through its interaction with tubulin and interferes with: amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca^2+ transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis	RR, 28%–36% PFS, 4.1 months OS, 22.9 months
Eribulin	Involves binding to a unique microtubule polymerization, without affecting depolymerization, and with additional sequestration of tubulin into nonfunctional aggregates	RR, 12% PFS, 3.7 months OS, 13.1 months

Abbreviations: OS, overall survival; PFS, progression-free survival; RR, response rate.

Table 2 Summary of most common grade 3/4 treatment-related adverse events from Phase II studies of eribulin

Adverse event n (%)	Vahdat et al (n = 103)	Cortes et al (n = 291)	Total (n = 394)
Fatigue	5 (5)*	29 (10)*	34 (9)
Alopecia	N/A	N/A	N/A
Neutropenia	66 (64)	157 (54)	223 (56.6)
Febrile neutropenia	4 (4)	19 (5.5)	20 (5.1)
Nausea	1 (1)*	6 (2.1)*	7 (1.7)
Anemia	1 (1)*	6 (2)	7 (1.7)

* Note: No grade 4.

Abbreviation: N/A, not available.

Table 3 Patient baseline characteristics in EMBRACE

	Eribulin % (n = 508)	TPC % (n = 254)	Total % (n = 762)
Median age (range)	55 (28–85)	56 (27–81)	55 (27–85)
ECOG performance status (%)
0–1	91	91	91
2	8	9	8
Estrogen receptor-positive (%)	66	67	67
Progesterone receptor-positive (%)	50	48	50
HER2 positive	16	16	16
Previous radiotherapy	83	77	81
Previous surgery	86	85	86
Number of organs involved
≤2	51	46	49
>2	49	54	51
Number of previous chemotherapy regimens
≤3	49	45	48
>3	53	55	53
Median	4 (1–7)	4 (2–7)	4 (1–7)
Previous treatment
Taxane	99	99	99
Capecitabine	73	74	73
Anthracycline	99	98	99
Refractory to Taxanes	81	80	81
Capecitabine	67	69	68
Anthracycline	56	61	58

Abbreviations: ECOG, Eastern Cooperative Oncology Group; EMBRACE, Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice versus Eribulin; HER2, human epidermal growth factor receptor 2; TPC, treatment of physician’s choice.

Table 4 Main grade 3/4 toxicities of eribulin in EMBRACE

	Grade 3	Grade 4
Hematological toxicity (%)
Neutropenia	21.1	41.1
Leukopenia	11.7	2.2
Anemia	1.8	0.2
Febrile neutropenia	3.0	1.2
Fatigue	8.2	0.6
Peripheral neuropathy	7.8	0.4
Dyspnea	3.6	0

Abbreviation: EMBRACE, Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice versus Eribulin.