Real-world treatment patterns and outcomes of abemaciclib for the treatment of HR+, HER2− metastatic breast cancer

Figures & data

Table 1. Baseline patient and clinical characteristics.

Characteristic, n (%) unless otherwise specified	Abemaciclib N = 118
Age at abemaciclib initiation, median (IQR)	66.5 (57.0, 73.0)
Age categories at index date
≤49 years	13 (11.0)
50–64 years	40 (33.9)
65–74 years	40 (33.9)
75–84 years	20 (16.9)
>85 years	5 (4.2)
Age at mBC diagnosis, median (IQR)	65.0 (55.2, 71.0)
Race
White	75 (63.6)
Black or African American	11 (9.3)
Asian	3 (2.5)
Other race	10 (8.5)
Unknown/missing	19 (16.1)
Practice type
Academic	2 (1.7)
Community	116 (98.3)
Age as a proxy for menopausal status^a
Post-menopausal (>60 years of age)	78 (66.1)
Pre-menopausal (≤60 years of age)	40 (33.9)
ER status^b
Negative	0 (0)
Positive	118 (100.0)
PR status^b
Negative	16 (13.6)
Positive	102 (86.4)
Modified Charlson Comorbidity Index status^c
0/unknown	85 (72.0)
1	20 (16.9)
2	10 (8.5)
3+	3 (2.5)
Stage at initial diagnosis
I	14 (11.9)
II	19 (16.1)
III	34 (28.8)
IV	41 (34.7)
Not documented	10 (8.5)
Tumor grade at initial diagnosis
Grade 1	11 (9.3)
Grade 2	54 (45.8)
Grade 3	27 (22.9)
Unknown/not documented	26 (22.0)
Time between initial and metastatic diagnosis^d
<2 years	16 (20.8)
≥2 years	61 (79.2)
ECOG PS^e at abemaciclib initiation
0	37 (31.4)
1	32 (27.1)
2	10 (8.5)
3	4 (3.4)
4	0 (0)
Unknown	35 (29.7)
Number of metastatic sites, median (IQR)	2.0 (1.0, 3.0)
Presence of metastases
Visceral metastases	58 (49.2)
Lung metastases	41 (34.7)
Liver metastases	27 (22.9)
Brain metastases	9 (7.6)
Bone metastases	97 (82.2)
Distant lymph node metastases	36 (30.5)
Other CNS metastases	4 (3.4)
Follow-up time, months, median (IQR)	6.4 (4.1, 9.5)

^aMenopausal status at index date was not available. A proxy for menopausal status was age, categorized as pre-menopausal (≤60 years of age), or post-menopausal (>60 years of age).

^bBiomarker status on or up to 60 days after the index date. In cases where a patient had multiple tests for a particular biomarker, results of the successful test closest to the index date were used.

^cExcludes cancer diagnosis.

^dAmong 77 patients who were not metastatic at initial diagnosis.

^eECOG PS may have been recorded up to 45 days prior to or up to 14 days after the index date, whichever was closest to the index date. If there were multiple ECOG PS values at the same absolute distance from the index date, priority was given to the ECOG PS preceding the index date. If there were multiple ECOG PS values recorded on the same day, the highest numerical value was selected. For confidentiality purposes, ECOG values of 5 were dropped.

Abbreviations: CNS, central nervous system; ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor; IQR, interquartile range; mBC, metastatic breast cancer; PR, progesterone receptor.

Table 2. Abemaciclib treatment regimens in a real-world setting.

Index abemaciclib line number, n (%)	Abemaciclib, N = 118	Abemaciclib + AI, n = 27	Abemaciclib + AI + Fulvestrant, n = 6	Abemaciclib + Fulvestrant, n = 70	Abemaciclib monotherapy, n = 15
1	34 (28.8)	11 (40.7)	3 (50.0)	18 (25.7)	2 (13.3)
2	25 (21.2)	5 (18.5)	2 (33.3)	18 (25.7)	0 (0)
3	24 (20.3)	5 (18.5)	1 (16.7)	17 (24.3)	1 (6.7)
4+	35 (29.7)	6 (22.2)	0 (0)	17 (24.3)	12 (80.0)

Abbreviations: AI, aromatase inhibitor.

Table 3. Abemaciclib treatment attributes in a real-world setting.

n (%), unless otherwise specified	Abemaciclib, N = 118	Abemaciclib + AI, n = 27	Abemaciclib + AI + Fulvestrant, n = 6	Abemaciclib + Fulvestrant, n = 70	Abemaciclib monotherapy, n = 15
Initial dose and schedule
50 mg, twice daily	4 (3.4)	0 (0.0)	0 (0.0)	2 (2.9)	2 (13.3)
100 mg, twice daily	5 (4.2)	0 (0.0)	0 (0.0)	5 (7.1)	0 (0.0)
150 mg, once daily	1 (0.8)	0 (0.0)	0 (0.0)	1 (1.4)	0 (0.0)
150 mg, twice daily	95 (80.5)	24 (88.9)	6 (100.0)	60 (85.7)	5 (33.3)
200 mg, once daily	1 (0.8)	1 (3.7)	0 (0.0)	0 (0.0)	0 (0.0)
200 mg, twice daily	9 (7.6)	2 (7.4)	0 (0.0)	1 (1.4)	6 (40.0)
Unknown	3 (2.5)	0 (0.0)	0 (0.0)	1 (1.4)	2 (13.3)
Experienced dose hold	44 (37.3)	13 (48.1)	3 (50.0)	23 (32.9)	5 (33.3)
Time to first dose hold, months, median (95% CI)	10.4 (2.5, NR)	3.9 (1.2, NR)	2.0 (1.8, NR)	10.4 (2.4, NR)	NR (1.6, NR)
Experienced dose reduction	8 (6.8)	1 (3.7)	0 (0.0)	4 (5.7)	3 (20.0)
Dose reduction amount
25 mg	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
50 mg	6 (75)	0 (0)	0 (0)	4 (100.0)	2 (66.7)
100 mg	2 (25.0)	1 (100.0)	0 (0)	0 (0)	1 (33.3)
200 mg	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Time to first dose reduction, months, median (95% CI)	NR (NR, NR)	NR (NR, NR)	NR (NR, NR)	NR (NR, NR)	6.7 (5.5, NR)
Experienced change in schedule	25 (21.2)	5 (18.5)	1 (16.7)	14 (20.0)	5 (33.3)
Change in schedule
Once daily to twice daily	2 (8)	1 (20.0)	0 (0)	1 (7.1)	0 (0)
Twice daily to once daily	18 (72.0)	3 (60.0)	0 (0)	11 (78.6)	4 (80.0)
Twice daily to other	5 (20.0)	1 (20.0)	1 (100.0)	2 (14.3)	1 (20.0)
Experienced discontinuation, n (%)	54 (45.8)	12 (44.4)	1 (16.7)	35 (50.0)	6 (40.0)
Time to first discontinuation, months, median (95% CI)	8.7 (4.5, NR)	8.7 (4.5, NR)	NR (NR, NR)	5.7 (3.6, NR)	3.3 (2.6, NR)

Abbreviations: AI, aromatase inhibitor; CI, confidence interval; NR, not reached.

Table 4. Real-world best response.

n (%)	Abemaciclib, n = 68^a	1 L Abemaciclib, n = 20	2 L Abemaciclib, n = 16	3 L Abemaciclib, n = 14	4 + L Abemaciclib, n = 18
Real-world BR	28 (41.2)	13 (65.0)	6 (37.4)	5 (35.7)	4 (22.3)
Real-world CR	4 (5.9)	1 (5.0)	1 (6.2)	1 (7.1)	1 (5.6)
Real-world PR	24 (35.3)	12 (60.0)	5 (31.2)	4 (28.6)	3 (16.7)
Real-world SD	23 (33.8)	6 (30.0)	5 (31.2)	4 (28.6)	8 (44.4)
Real-world PD	17 (25.0)	1 (5.0)	5 (31.2)	5 (35.7)	6 (33.3)

^aAmong all abemaciclib patients (N = 118) who had at least one real-world response assessment.

Abbreviations: 1 L, first line; 2 L, second line; 3 L, third line; 4 + Line, ≥fourth line; BR, best response; CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.

Figure 1. Real-world progression-free survival. Abbreviations. rwPFS, real-world progression-free survival.

Table 5. Real-world adverse effects of interest during index therapy (new or worsening event) and medical history of these real-world adverse events.

rwAE of interest, n (%) unless otherwise stated	Abemaciclib
	N = 118
Any rwAE during index therapy	95 (80.5)
Any rwAE at baseline or as part of medical history	15 (12.7)
Diarrhea during index therapy
Physician assessed any-grade diarrhea^a	79 (67.0)
Diarrhea at baseline^b	5 (6.3)
Hospitalization due to diarrhea	8 (6.8)
Medication for diarrhea	55 (46.6)
Therapy^c discontinuation due to diarrhea	14 (11.9)
Therapy^c dose or schedule change due to diarrhea	15 (12.7)
Therapy^c hold due to diarrhea	17 (14.4)
Neutropenia during index therapy
Any grade	43 (36.4)
Grade 3 or 4	9 (7.6)
Medical history of neutropenia^d	4 (9.3)
Grade 1^e	1 (25.0)
Grade 2^e	2 (50.0)
Grade 3^e	1 (25.0)
Neutropenia grade change (baseline → index)
Grade 1 → Grade 2^e	1 (25.0)
Grade 2 → Grade 4^e	1 (25.0)
No neutropenia → Grade 1	11 (9.3)
No neutropenia → Grade 2	20 (16.9)
No neutropenia → Grade 3	8 (6.8)
Filgrastim/pegfilgrastim use^f	3 (2.5)
During index therapy before onset of neutropenia^g	2 (1.7)
During index therapy after onset of neutropenia^h	2 (1.7)
Any elevated liver enzymes during index therapy
Any grade	9 (7.6)
Grade 3	2 (1.7)
Medical history of elevated liver enzymes^i	5 (55.6)
Grade 1^j	3 (60.0)
Grade 2^j	2 (40.0)
Liver enzyme elevation grade change (baseline → index)
Grade 1 → Grade 2^i	2 (22.2)
Grade 1 → Grade 3^i	1 (11.1)
No elevated liver enzymes → Grade 2	3 (2.5)
No elevated liver enzymes → Grade 3	1 (0.8)
Any AST elevation during index therapy	3 (2.5)
Grade 2	2 (1.7)
Grade 3	1 (0.8)
Any AST elevation during Baseline	22 (18.6)
Grade 1	15 (12.7)
Grade 2	1 (0.8)
Grade 3	3 (2.5)
Grade 4	3 (2.5)
AST grade change (baseline → index)	2 (1.7)
No AST → Grade 2	1 (0.8)
No AST → Grade 3	1 (0.8)
Any ALT elevation during index therapy	3 (2.5)
Grade 2	1 (0.8)
Grade 3	2 (1.7)
Any ALT elevation during Baseline	88 (74.6)
Grade 1	88 (74.6)
ALT grade change (baseline → index)
Grade 1 → Grade 2	1 (0.8)
Grade 1 → Grade 3	2 (1.7)
ALT elevation Grade ≥2 with Total Bilirubin Grade ≥2 during index therapy	1 (0.8)
ALT elevation Grade ≥2 without Total Bilirubin Grade ≥2 during index therapy	2 (1.7)
Any bilirubin during index therapy	4 (3.4)
Grade 2	4 (3.4)
Bilirubin grade change (baseline → index)
No bilirubin → Grade 2	3 (2.5)
VTE during index therapy
Physician assessed any-grade VTE	4 (3.4)
VTE at baseline^k	1 (25.0)
Hospitalization due to VTE	1 (0.8)
Medication for VTE	4 (3.4)
Therapy hold due to VTE	0 (0)

^aGrade was not available for diarrhea. Outcomes for diarrhea were not mutually exclusive.

^bAmong patients who had diarrhea during index therapy.

^cTherapy discontinuations, dose or schedule changes, or dose holds could be any part of therapy (e.g. abemaciclib or a combination therapy).

^dAmong patients who had neutropenia during index therapy.

^eAmong patients who had a medical history of neutropenia.

^fSub-categories of filgrastim/pegfilgrastim use are not mutually exclusive.

^gAmong those with neutropenia during index therapy, filgrastim/pegfilgrastim use during index, before the initial onset of neutropenia.

^hAmong those with neutropenia during index therapy, filgrastim/pegfilgrastim use during index therapy on or after the initial onset of derived neutropenia.

ⁱAmong patients who had elevated liver enzymes during index therapy.

^jAmong patients who had a medical history of elevated liver enzymes.

^kAmong patients who had VTE during index therapy.

Abbreviations. ALT, alanine aminotransferase; AST, aspartate aminotransferase; rwAE, real-world adverse event; VTE, venous thromboembolic event.

Data availability statement

The data that support the findings of this study have been originated by Flatiron Health, Inc. These de-identified data may be made available upon request, and are subject to a license agreement with Flatiron Health; interested researchers should contact <[email protected]> to determine licensing terms.