Observational Study of Clinical Outcomes of Eribulin Mesylate in Metastatic Breast Cancer After Cyclin-Dependent Kinase 4/6 Inhibitor Therapy

Figures & data

Figure 1. Study period.

^†Patients may have still been receiving eribulin at the time of data cutoff.

Figure 2. Eribulin utilization patterns and study cohort flow diagram.

Table 1. Demographics and clinical characteristics at metastatic breast cancer diagnosis, and cyclin-dependent kinase 4/6 inhibitor utilization.

Demographic and clinical variables	All (n = 395)	Cohort 1 (n = 121)	Cohort 2 (n = 111)	Cohort 3 (n = 135)	Cohort 4 (n = 28)
Race:
White/Caucasian	258 (65.3%)	79 (65.3%)	76 (68.5%)	81 (60.0%)	22 (78.6%)
Black/African–American	97 (24.6%)	31 (25.6%)	23 (20.7%)	38 (28.2%)	5 (17.9%)
Asian	28 (7.1%)	6 (5.0%)	11 (9.9%)	10 (7.4%)	1 (3.6%)
Other	12 (3.3%)	5 (4.1%)	1 (0.9%)	6 (4.4%)	0 (0.0%)
Stage IV at diagnosis	251 (63.5%)	93 (76.9%)	64 (57.7%)	78 (57.8%)	16 (57.1%)
Visceral metastatic disease at mBC diagnosis (n, %)
Yes	275 (69.6%)	86 (71.1%)	75 (67.6%)	98 (72.6%)	16 (57.1%)
Bone only	120 (30.4%)	35 (28.9%)	36 (32.4%)	37 (27.4%)	12 (42.9%)
CDK 4/6i line of therapy
First	283 (71.7%)	121 (100%)	81 (73.0%)	68 (50.4%)	13 (46.4%)
Second	71 (18.0%)	0 (0%)	30 (27.0%)	35 (25.9%)	6 (21.4%)
≥Third	41 (10.4%)	0 (0%)	0 (0%)	32 (23.7%)	9 (32.1%)
CDK 4/6i agent
Palbociclib plus endocrine therapy	349 (88.4%)	102 (84.3%)	95 (85.6%)	125 (92.6%)	27 (96.4%)
Palbociclib plus letrozole	189 (47.9%)	67 (55.4%)	35 (31.5%)	71 (52.6%)	16 (57.1%)
Palbociclib plus fulvestrant	116 (29.4%)	22 (18.2%)	50 (45.1%)	37 (27.4%)	7 (25.0%)
Palbociclib plus other (e.g., exemestane, anastrozole, etc.)	44 (11.1%)	13 (10.7%)	10 (9.0%)	17 (12.6%)	4 (14.0%)
Ribociclib	27 (6.8%)	12 (9.9%)	6 (5.4%)	9 (6.7%)	0 (0.0%)
Abemaciclib	14 (3.5%)	6 (5.0%)	7 (6.3%)	1 (0.7%)	0 (0.0%)
Palbociclib or abemaciclib without hormonal therapy indicated	5 (1.3%)	1 (0.8%)	3 (2.7%)	0 (0.0%)	1 (3.6%)
Mean duration (months) of CDK 4/6i (median)^â€	11.0 (9.7)	12.9 (12.2)	9.9 (9.5)	10.1 (9.1)	11.5 (9.9)
Mean months of follow-up from initiation of first-line therapy in the metastatic setting (SD)	28.8 (12.4)	24.3 (8.7)	26.2 (11.7)	33.3 (13.0)	36.6 (14.7)

† All patients had discontinued CDK 4/6i therapy to be eligible for inclusion in the study.

mBC: Metastatic breast cancer; SD: Stable disease.

Table 2. Patient characteristics at the initiation of eribulin.

Patient characteristics	All (n = 395)	Cohort 1 (n = 121)	Cohort 2 (n = 111)	Cohort 3 (n = 135)	Cohort 4 (n = 28)
Mean age at initiation of eribulin (SD)	64.8 (9.1)	65.5 (9.9)	65.4 (8.9)	63.4 (8.4)	66.6 (9.0)
Sites of metastatic disease at initiation of eribulin (n, %)
Adrenal gland	34 (8.6%)	16 (13.2%)	12 (10.8%)	5 (3.7%)	1 (3.6%)
Bone	248 (62.8%)	78 (64.5%)	64 (57.7%)	84 (62.2%)	22 (78.6%)
Brain	17 (4.3%)	4 (3.3%)	4 (3.6%)	9 (6.7%)	0 (0.0%)
Distant lymph nodes	99 (25.1%)	37 (30.6%)	23 (20.7%)	31 (23.0%)	8 (26.8%)
Liver	186 (47.1%)	47 (38.8%)	56 (50.5%)	70 (51.9%)	13 (46.4%)
Lung	215 (54.4%)	68 (56.2%)	62 (55.9%)	76 (56.3%)	9 (32.1%)
Pleura, pericardial and/or peritoneal cavity	20 (5.1%)	6 (5.0%)	8 (7.2%)	5 (3.7%)	1 (3.6%)
Other^â€	11 (2.8%)	3 (2.5%)	2 (1.8%)	5 (3.7%)	2 (7.1%)
Visceral metastatic disease at mBC diagnosis (n, %)
Yes	345 (89.6%)	105 (86.8%)	101 (91.0%)	125 (92.6%)	23 (82.1%)
Bone only	41 (10.4%)	16 (13.2%)	10 (9.0%)	10 (7.4%)	5 (17.9%)
ECOG-PS at initiation of eribulin (n, %)
0/1	303 (76.7%)	92 (76.0%)	90 (81.1%)	107 (79.3%)	14 (50.0%)
≥2	91 (23.0%)	28 (23.1%)	21 (18.9%)	28 (20.7%)	14 (50.0%)
Unknown	1 (0.3%)	1 (0.8%)	0 (0.0%)	0 (0.0%)	0 (0.0%)

† Including gastrointestinal, genitourinary, gynecological or other sites not specified.

ECOG-PS: Eastern Cooperative Oncology Group performance status; mBC: Metastatic breast cancer; SD: Stable disease.

Table 3. Duration of eribulin treatment, rationale for discontinuation, objective disease response to eribulin and progression-free survival.

Patient outcomes	All (n = 395)	Cohort 1 (n = 121)	Cohort 2 (n = 111)	Cohort 3 (n = 135)	Cohort 4 (n = 28)
Mean duration (months) of eribulin treatment (median)^â€	3.8 (3.0)	4.7 (3.6)	3.5 (2.9)	3.6 (2.9)	2.7 (2.9)
Status at end of follow-up (n, %)
Still receiving eribulin treatment	246 (62.3%)	66 (54.6%)	83 (74.8%)	86 (63.7%)	11 (39.3%)
Discontinued eribulin treatment	149 (37.8%)	55 (45.5%)	28 (25.2%)	49 (36.3%)	17 (60.7%)
Deceased	60 (15.2%)	16 (13.2%)	12 (10.8%)	28 (20.7%)	4 (14.3%)
Rationale for discontinuation of eribulin (% of discontinued)
Schedule duration of therapy completed	8 (5.4%)	3 (5.5%)	2 (7.1%)	2 (4.1%)	1 (5.9%)
Disease progression	77 (51.7%)	30 (54.5%)	15 (53.6%)	18 (36.7%)	14 (82.4%)
Toxicity/adverse event	6 (4.0%)	1 (1.8%)	2 (7.1%)	2 (4.1%)	1 (5.9%)
Patient request	31 (20.8%)	9 (16.4%)	5 (17.9%)	17 (34.7%)	0 (0.0%)
Financial challenges	4 (2.7%)	4 (7.3%)	0 (0%)	0 (0%)	0 (0.0%)
Patient died	4 (2.7%)	2 (3.6%)	0 (0%)	1 (2.0%)	1 (5.9%)
Do not know/other	19 (12.7%)	6 (10.9%)	4 (14.3%)	9 (18.4%)	0 (0.0%)
Disease response (n, %)
Objective response rate (CR+PR)^‡	121 (30.6%)	51 (42.2%)	29 (26.1%)	36 (26.7%)	5 (17.9%)
Clinical benefit rate (CR+PR+SD)^‡	204 (51.6%)	71 (58.7%)	47 (42.3%)	73 (54.1%)	13 (46.4%)
Not evaluated	153 (38.7%)	40 (33.1%)	57 (51.4%)	48 (35.6%)	8 (28.6%)
Complete response	1 (0.3%)	0 (0.0%)	1 (0.9%)	0 (0.0%)	0 (0.0%)
Partial response	120 (30.4%)	51 (42.2%)	28 (25.2%)	36 (26.7%)	5 (17.9%)
Stable disease	83 (21.0%)	20 (16.5%)	18 (16.2%)	37 (27.4%)	8 (26.8%)
Stable disease >6 months	16 (4.1%)	7 (4.7%)	3 (2.7%)	6 (4.4%)	0 (0.0%)
Progressive disease	38 (9.6%)	10 (8.3%)	7 (6.3%)	14 (10.4%)	7 (25.0%)
Median PFS (95% CI)^§	10.3 (7.8–17.5)	9.7 (7.7–17.5)	10.3 (7.3–NR)	NR	4.0 (3.2–4.4)
6-Month PFS rate (95% CI)^§	68.8% (60.8–74.7%)	77.3% (67.3–87.4%)	71.3% (56.8–85.7%)	70.4% (58.5–82.3%)	0.0%^¶

† Among all patients including those still receiving eribulin at data cutoff.

‡ Includes patients for whom disease response had not yet been evaluated.

§ Estimated using the Kaplan–Meier method.

¶ All patients had progressed in cohort 4 by the start of month 6.

CR: Complete response; PFS: Progression-free survival; PR: Partial response; SD: Stable disease.

Table 4. Occurrence of selected toxicities during eribulin treatment.^†

Toxicity	All (n = 395)	Cohort 1 (n = 121)	Cohort 2 (n = 111)	Cohort 3 (n = 135)	Cohort 4 (n = 28)
Neutropenia (n, %)	93 (23.5%)	27 (22.3%)	29 (26.1%)	31 (23.0%)	6 (21.4%)
Grade 3/4	32 (34.4%)	9 (33.3%)	12 (41.4%)	9 (29.0%)	2 (33.3%)
Patients with prior neutropenia (within 3 months of eribulin start)	54 (58.1%)	19 (70.4%)	13 (44.8%)	18 (58.1%)	4 (66.7%)
Febrile neutropenia (n, %)	5 (1.3%)	3 (2.5%)	1 (0.9%)	1 (0.7%)	0 (0.0%)
Peripheral neuropathy (n, %)	40 (10.1%)	10 (8.3%)	13 (11.7%)	15 (11.1%)	2 (7.1%)
Grade 2/3/4	23 (57.5%)	6 (60.0%)	7 (53.8%)	9 (60.0%)	1 (50.0%)
Diarrhea (n, %)	44 (11.1%)	14 (11.6%)	11 (9.9%)	17 (12.6%)	2 (7.1%)
Grade 3/4	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)
Received growth factor during eribulin treatment (n, %)	48 (12.2%)	11 (9.1%)	16 (14.4%)	16 (11.9%)	5 (17.9%)

† Anytime, grade 3/4 proportion among those experiencing the toxicity.