Potential clinical applications of halichondrins in breast cancer and other neoplasms

Figures & data

Figure 1 Molecular structure of halichondrin B and eribulin mesylate (E7389). Kuznetsov et al. Cancer Res. 2004.

Table 1 Phase II trials with eribulin mesylate in metastatic breast cancer patients

Trial	N	ORR (%)	CBR (%)	Median DOR (months)	Median PFS (months)	Median OS (months)	6-month PFS (%)	6-month OS (%)	Grade 3/4 toxicities
Vahdat et al^Citation26	87	11.5	17.2	5.6	2.6	9	25.9	67.8	Neutropenia, leukopenia, fatigue
Cortes et al^Citation27	269	9.3	17.1	4.1	2.6	10.4	12.4	72.3	Neutropenia, leukopenia, fatigue
Iwata et al^Citation28	81	21.3	27.5	3.9	3.7	11	20.1	72.3	Neutropenia, leukopenia, febrile neutropenia

Abbreviations: ORR, overall objective response rate; CBR, clinical benefit rate; DOR, duration of response; PFS, progression-free survival; OS, overall survival.

Table 2 Adverse events with an incidence >10% in eribulin treatment group and treatment of physician’s choice in EMBRACE Phase III trial in metastatic breast cancer

	Eribulin (n = 503)			TPC (n = 247)
	All grades	Grade 3	Grade 4	All grades	Grade 3	Grade 4
Hematological
Neutropenia^†	260 (52%)	106 (21%)	121 (24%)	73 (30%)	35 (14%)	17 (7%)
Leucopenia	116 (23%)	59 (12%)	11 (2%)	28 (11%)	12 (5%)	2 (1%)
Anemia	94 (19%)	9 (2%)	1 (<1%)	56 (23%)	8 (3%)	1 (<1%)
Non-hematological
Asthenial/fatigue	270 (54%)	41 (8%)	3 (1%)	98 (40%)	25 (10%)	0
Alopecia	224 (45%)	–	–	24 (10%)	–	–
Peripheral neuropathy^‡	174 (35%)	39 (8%)	2 (<1%)	40 (16%)	5 (2%)	0
Nausea	174 (35%)	6 (1%)	0	70 (28%)	6 (2%)	0
Constipation	124 (25%)	3 (1%)	0	51 (21%)	2 (1%)	0
Arthralgia/myalgia	109 (22%)	2 (<1%)	0	29 (12%)	3 (1%)	0
Weight loss	107 (21%)	3 (1%)	0	35 (14%)	1 (<1%)	0
Pyrexia	105 (21%)	1 (<1%)	0	31 (13%)	1 (<1%)	0
Anorexia	98 (19%)	2 (<1%)	0	32 (13%)	3 (1%)	0
Headache	97 (19%)	2 (<1%)	0	29 (12%)	0	1 (<1%)
Diarrhea	92 (18%)	0	0	45 (18%)	0	0
Vomiting	91 (18%)	4 (1%)	1 (<1%)	44 (18%)	3 (1%)	0
Back pain	79 (16%)	3 (1%)	1 (<1%)	18 (7%)	3 (1%)	1 (<1%)
Dyspnea	79 (16%)	18 (4%)	0	31 (13%)	6 (2%)	1 (<1%)
Cough	72 (14%)	0	0	21 (9%)	0	0
Bone pain	60 (12%)	9 (2%)	0	23 (9%)	4 (2%)	0
Pain in extremity	57 (11%)	5 (1%)	0	25 (10%)	3 (1%)	0
Mucosal inflammation	43 (9%)	7 (1%)	0	25 (10%)	5 (2%)	0
Palmar-plantar erythrodysaesthesia	7 (1%)	2 (<1%)	0	34 (14%)	9 (4%)	0

Abbreviation: EMBRACE, Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice Versus E7389 (NCT00388726; E 305). With permission: Cortes et al. Lancet. 2011.

VahdatLTPruittBFabianCJPhase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxaneJ Clin Oncol2009272954296119349550

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