Thromboembolic Events in Patients with HER2-Negative, Hormone Receptor-Positive, Metastatic Breast Cancer Treated with Ribociclib Combined with Letrozole or Fulvestrant: A Real-World Data

Figures & data

Table 1 Patients’ Characteristics (n=305)

Characteristics		Number	Percentage
Age (Years)	Median (Range) Years	49 (22–87)
	< 40	52	17.0
	40–49	104	34.1
	50–59	75	24.6
	60–69	54	17.7
	≥ 70	20	6.6
Gender	Female	302	99.0
	Male	3	0.98
Timing of metastasis	De novo	168	55.1
	Recurrent	137	44.9
Site of metastasis	Bone	241	79.0
	Bone-only	119	39.0
	Liver	67	22.0
	Lung	79	25.9
	Brain	17	5.6
	Serosal surfaces	49	16.1
	Bone marrow	5	1.6
Number of metastatic sites	1	127	41.6
	2	108	35.4
	3	42	13.8
	≥ 4	28	9.2
Smoking history	Current smoker	30	9.8
	Prior smoker	15	4.9
	Never smoked	219	71.8
	Unknown	41	13.4
Pathology	IDC	245	80.3
	ILC	46	15.1
	Others	14	4.6
Tumor grade	I	22	7.2
	II	173	56.7
	III	89	29.2
	NA	21	6.9
ECOG performance status	Zero	192	63.0
	1	97	31.8
	2	10	3.3
	3–4	2	0.6
	NA	4	1.3

Abbreviations: IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; NA, not available; ECOG, Eastern Cooperative Oncology Group.

Table 2 Endocrine Therapy

Characteristics		Number	Percentage
Line of therapy	First Line	195	63.9
	Beyond first line	110	36.1
Companion ET	Letrozole	195	63.9
	Fulvestrant	110	36.1
Duration of ribociclib therapy (months)	Median (Range)	7 (1–45)
	< 6 Months	139	45.5
	6–12 Months	66	21.6
	12–18 Months	44	14.4
	≥ 18 Months	56	18.4
Ribociclib dose reduction	Yes	44	14.4
	No	261	85.6
Response to ribociclib	Complete response (CR)	1	0.3
	Partial response (PR)	105	34.4
	Stable disease (SD)	72	23.6
	Disease progression (DP)	68	22.2
	Not available	59	19.3

Abbreviation: ET, endocrine therapy.

Table 3 Confirmed Cases of Thromboembolic Events

Case Number	Age (Years)	Smoking	Site of VTE	Time to TEE	Endocrine Therapy Companion	Type of Metastasis	Metastatic Site	Other Risk Factors for TEE
1	43	No	Lateral sinus thrombosis	6 months	AI/GnRHa	Recurrent	Brain, Lymph Nodes	Cancer diagnosis < 6 months
2	64	No	Bilateral PE	3 months	AI	De novo	Bone, Leptomeningeal, Bone Marrow	Cancer diagnosis < 6 months,
3	65	No	Bilateral PE	1 month	Fulvestrant	De Novo	Peritoneal Ascites	Hospital admission within 30 days of TEE
4	67	Yes	Superior sagittal sinus thrombosis	15 days	AI	De Novo	Bone, Liver, Pleura	Cancer diagnosis < 6 months Dyslipidemia, Diabetes
5	77	Yes	PE	3 months	AI	Recurrent	Bone	Cancer diagnosis < 6 months
6	77	Yes	Lower limb ischemia	1 month	AI	Recurrent	Lung, Bone, Pleural effusion	Cancer diagnosis < 6 months

Abbreviations: TEE, thromboembolic events; AI, aromatase inhibitors; GnRHa, gonadotropin releasing hormone agonists; PE, pulmonary embolism.

Table 4 Summary of Published Studies

Clinical Trial	Study Arms	Number of Patients Included	End Point	Thrombosis Rate	Relative Risk (RR) 95% CI	P-value
All CDK4/6 inhibitors	CDK4/6 arms	2793	VTE	56 (2%)	2.62 1.21–5.65	0.01
	Control	1764		10 (0.5%)
PALOMA	Palbociclib	872	VTE	14 (1.6%)	2.33 0.36–15.19	0.38
	Control	471		3 (0.6)
MONALEESA	Ribociclib	1153	VTE	13 (1.12%)	2.19 0.80–5.97	0.13
	Control	909		5 (0.55%)
MONARCH	Abemaciclib	768	VTE	29 (3.77%)	6.77 1.61–28.43	0.009
	Control	384		2 (0.5%)

Note: Data from Thein et al.³¹

Abbreviations: CI, confidence interval; CDK4/6, cyclin dependent kinase; VTE, venous thromboembolism.

Thein KZ, Htut TW, Ball S, Swarup S, Sultan A, Oo TH. Venous thromboembolism risk in patients with hormone receptor-positive HER2-negative metastatic breast cancer treated with combined CDK 4/6 inhibitors plus endocrine therapy versus endocrine therapy alone: a systematic review and meta-analysis of randomized controlled trials. Breast Cancer Res Treat. 2020;183(2):479–487. doi:10.1007/s10549-020-05783-3

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