A retrospective safety and efficacy analysis of the first patients treated with eribulin for metastatic breast cancer in Stockholm, Sweden

Figures & data

Table I. Baseline characteristics of the 48 patients with metastatic breast cancer treated with eribulin.

Age at treament start; median (range)	56 (35–74)
ECOG
0	36 (75%)
1	7 (15%)
2	5 (10%)
Radiology assessment*
Yes	38 (79%)
No	10 (21%)
Neo/adjuvant chemotherapy
Yes	41 (85%)
No	7 (15%)
Previous chemotherapy in metastatic setting
Anthracyclines	25 (52%)
Taxanes	39 (81%)
Capecitabine	43 (90%)
Treatment line** with eribulin (%)
2nd	4 (8%)
3rd	13 (27%)
4th	14 (29%)
5th	6 (12.5%)
6th	6 (12.5%)
7th	3 (6%)
8th	2 (4%)
Dose reduction during treatment (%)	30 (62.5%)
Number of courses of eribulin; median (range)	7 (1–21)

*at baseline and at least one follow-up using the same modality; **refers to chemotherapy for metastatic disease.

Figure 1. Kaplan-Meyer estimates of (a) overall survival (OS) and (b) progression-free survival (PFS) in 48 patients with metastatic breast cancer who received up to three versus ≥ 4 previous chemotherapies before treatment with eribulin at the Department of Oncology, Karolinska University Hospital, Stockholm.

Table II. Eribulin treatment-related adverse events.

Event*	All grades n (%)	Grade 1/2 n (%)	Grade 3/4 n (%)
Neutropenia	13 (27%)	4 (8.4%)	9 (18.8%)
Neurotoxicity	13 (27%)	12 (25%)	1 (2.1%)
Infection	8 (16.7%)	5 (10.4%)	3 (6.2%)
Fatigue	48 (100%)	45 (93.8%)	3 (6.2%)
Hospitalization	9 (18%)	NA	NA
Discontinuation of treatment	4 (8%)	NA	NA

NA, not applicable.

*Scaled according to National Cancer Institute – Common Toxicity Criteria for Adverse Events v 4.0.

Table III. Histopathological characteristics of primary tumor and corresponding metastasis in 48 patients with breast cancer treated with eribulin.

	Primary tumor n (%)	Metastasis n (%)
	48 (100%)	48 (100%)
ER status
positive	34 (70.8%)	29 (60.4%)
negative	12 (25%)	12 (25%)
unknown	2 (4.2%)	7 (14.6%)
PR status
positive	22 (45.8%)	16 (33.3%)
negative	20 (41.7%)	24 (50%)
unknown	6 (12.5%)	8 (16.7%)
HER2 status
positive	8 (16.7%)	5 (10.4%)
negative	27 (56.3%)	29 (60.4%)
unknown	13 (27.1%)	14 (29.2%)
Ki67
low	12 (25%)	13 (27.1%)
high	23 (47.9%)	14 (29.2%)
unknown	13 (27.1%)	21 (43.8%)
TNBC*
yes	6 (12.5%)
no	42 (87.5%)
Tumor grade
low	3 (6.3%)
intermediate	17 (35.4%)
high	24 (50%)
unknown	4 (8.3%)

ER, estrogen receptor; HER2, Human Epidermal Growth Factor 2 receptor; PR, progesterone receptor; TNBC, triple negative breast cancer.

*TNBC status is defined according to ER, PR or HER2 in metastasis when the status is missing in primary tumor.

Table IV. Efficacy analysis in subgroups of patients identified according to ER, HER2 and Ki67 expression.

		OS		PFS		ORR n (%)	CBR n (%)
	n	Events	Median (months)	Events	Median (months)
ER*
positive	36	22	8.9	31	5.2	15 (42%)	18 (50%)
negative	12	7	8.1	11	3.9	2 (17%)	5 (42%)
HER2**
positive	9	4	9.2	7	4.3	1 (11%)	4 (44%)
negative	38	24	8.7	34	5	16 (42%)	19 (50%)
Ki67
low	12	7	10.9	9	4.9	4 (33%)	6 (50%)
high	23	15	7.3	20	4.4	7 (30%)	10 (43%)
TNBC
yes	6	4	5.6	6	2.1	0 (0%)	1 (17%)
no	42	25	9.2	36	5	17 (41%)	22 (52%)

CBR, clinical benefit rate; ER, estrogen receptor; HER2, Human Epidermal Growth Factor 2 receptor; n, number of patients; ORR, objective response rate; OS, overall survival; PFS, progression free survival; TNBC, triple negative breast cancer.

*ER status is evaluated in primary tumor tissue in 46 patients and in metastatic tissue in 2 patients; **HER2 status is evaluated in primary tumor tissue in 35 patients and in metastatic tissue in 12 patients.

Table V. Summary of published data on eribulin treatment in locally recurrent and metastatic breast cancer.

Study design	N	Population and design	Dose and schedule*	Efficacy	Toxicities	Ref
Phase II trials
Vahdat et al. (2009)	103 (per protocol = 87)	Open-label, single arm, Simon’s two- stage, multicenter; patients with metastatic breast cancer previously treated with at least an anthracycline and a taxane	Eribulin mesylate 1.4 mg/m^2 infusion on days 1, 8 and 15 of a 28-day or on days 1 and 8 of a 21-day cycle	ORR, 10.2% and 14.3% in 28-day and 21-day group, respectively (per protocol); CBR, 11.9% and 28.6%, in 28-day and 21-day group, respectively (per protocol); median PFS, 2.6 months; median OS, 9 months.	Grade 3/4: neutropenia, 64%; leukopenia, 18%; fatigue, 5%; peripheral neuropathy, 5%; febrile neutropenia, 4%	7
Cortes et al. (2010)	291	Open-label, single arm, multicenter; patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline, a taxane and capecitabine	Eribulin mesylate 1.4 mg/m^2 infusion on days 1 and 8 of a 21-day cycle	ORR, 9.3%; CBR, 17.1%; median DOR, 4.1 months, median PFS, 2.6 months; median OS, 10.4 months	Grade 3/4: neutropenia, 54%; leukopenia, 14%; asthenia or fatigue, 10% (no grade 4); neuropathy, 6.9% (no grade 4)	6
Aogi et al. (2012)	80	Open-label, single arm, multicenter; patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane	Eribulin mesylate 1.4 mg/m^2 infusion on days 1 and 8 of a 21-day cycle	ORR, 21.3%; CBR, 27.5% ; median DOR, 3.9 months; median PFS, 3, 7; median OS, 11.1 months	Grade 3/4: neutropenia, 95.1%; leukopenia, 74.1%; febrile neutropenia, 13.6%; peripheral neurophaty, 3.7% (only grade 3)	8
McIntyre et al. (2014)	56	Open-label, single arm, multicenter; patients with locally recurrent or metastatic HER2-negative breast cancer previously untreated in the advanced setting	Eribulin mesylate 1.4 mg/m^2 infusion on days 1 and 8 of a 21-day cycle	ORR, 29%; CBR, 52%, median DOR, 5.8 months; median PFS, 6.8 months	Grade 3/4: neutropenia, 50%; leukopenia, 21%; peripheral neuropathy, 21%	9
Phase III trials
Cortes et al. (2011)	762	Open-label, randomized; patients with locally recurrent or metastatic breast cancer previously receiving two to five regimens including an anthracycline and a taxane	Eribulin mesylate 1.4 mg/m^2 infusion on days 1 and 8 of a 21-day cycle or TPC	Median OS, 13.1 in eribulin grous vs. 10.6 months in TPC group (p = 0.041); median PFS, 3.7 in eribulin grous vs. 2.2 months in TPC group (p = −0.137); ORR, 12% with eribulin vs. 5% with TPC (p = 0.002)	Adverse events, 99% in eribulin group and 93% in TPC group. Grade 3/4events: neutropenia 21% vs. 14%; leucopenia 12% vs. 5%; peripheral neuropathy 8% vs. 2% in eribulin group and in TPC group, respectively	10
Others
Hattori et al. (2013)	27	Restrospective study	Eribulin monotherapy	ORR, 25.9%; CBR, 29.6%; median PFS 9.9 weeks.		14
Ramaswami et al. (2014)	25	Institution experience report; unselected cohort of locally recurent or metastatic breast cancer patients	Eribulin mesylate 1.4 mg/m^2 infusion on days 1 and 8 of a 21-day cycle	ORR, 18%; CBR, 41%; median TTP, 4.08 months; median OS, 5.89 months	Neuropathy grade 3, 4%	13
Poletti et al. (2014)	27	Institution experience report; unselected cohort of locally recurent or metastatic breast cancer patients	Eribulin mesylate 1.4 mg/m^2 infusion on days 1 and 8 of a 21-day cycle	DCR, 44.4%; CBR, 66.7%; median DOR, 2.5 months; median OS; 8 months	Neutropenia grade 3, 7%	15
Gamucci et al (2014)	133	Multicenter observational retrospective study;patients with advanced breast cancer who received ≥ 2 chemotherapy lines	Eribulin mesylate 1.4 mg/m^2 infusion on days 1 and 8 of a 21-day cycle	ORR, 21.1%; CBR, 38.3%: median DOR, 5.2 month; median PFS, 4.4 months; median OS, 14.3 months	Neutropenia, grade 3, 14.3%; neurotoxicity, 3.8%	16

CBR, clinical benefit rate; DCR, disease control rate; DOR, duration of response; N, number of patients; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TPC, treatment of physician’s choice; TTP, time-to-progression.