Biosimilar Retacrit^® (epoetin zeta) in the treatment of chemotherapy-induced symptomatic anemia in hematology and oncology in Germany (ORHEO) – non-interventional study

Figures & data

Table 1 Demographics and baseline clinical characteristics

Parameter	Lymphoma/myeloma (N=30)	Breast cancer (N=95)	Other solid tumors (N=165)	Total (N=290)
Gender, n (%)
Male	17 (56.7)	2 (2.13)	69 (41.8)	88 (30.4)
Female	13 (43.3)	92 (97.9)	96 (58.2)	201 (69.6)
Mean age (SD), years*	69.5 (15.2)	60.2 (11.9)	69.2 (10.4)	66.2 (12.2)
Median age (min, max)	75.5 (32, 86)	61 (29, 88)	72 (37, 89)	69 (29, 89)
Mean body weight (SD), kg	73.2 (16.2)	70.2 (12.4)	71.1 (13.9)	71.0 (13.6)
Mean height (SD), cm	168.7 (9.3)	165.6 (5.9)	167.5 (8.3)	167.0 (7.8)
Mean diastolic blood pressure (SD), mmHg	77.5 (6.0)	80.0 (10.1)	75.9 (10.4)	77.6 (10.2)
Mean systolic blood pressure (SD), mmHg	127.8 (8.1)	128.8 (14.9)	129.3 (15.6)	129.0 (14.9)

Note:

* Age: 2013 minus birth year.

Abbreviation: SD, standard deviation.

Table 2 ECOG/WHO status stratified by disease (all) and metastatic status (breast cancer patients)

ECOG status	Lymphoma/myeloma (N=30) (%)	Breast cancer (N=95) (%)	Other solid tumors (N=165) (%)	Total (N=290) (%)
0	5 (16.7)	29 (30.5)	29 (17.6)	63 (21.7)
1	20 (66.7)	59 (62.1)	112 (67.9)	191 (65.9)
2	4 (13.3)	7 (7.4)	19 (11.5)	30 (10.3)
3	1 (3.3)	0	5 (3.0)	6 (2.1)
ECOG status	Non-metastatic (N=65) (%)	Metastatic (N=21) (%)	Not determined (N=9) (%)	Total (N=95) (%)
0	24 (36.9)	4 (19.0)	1 (11.1)	29 (30.5)
1	40 (61.5)	12 (57.1)	7 (77.8)	59 (62.1)
2	1 (1.5)	5 (23.8)	1 (11.1)	7 (7.4)
3	0	0	0	0

Table 3 Hemoglobin stratified by disease at study entry

Hemoglobin (g/dL)	Lymphoma/myeloma (N=30) (%)	Breast cancer (N=95) (%)	Other solid tumors (N=165) (%)	Total (N=290) (%)
≤9	11 (36.7)	13 (13.8)	34 (20.6)	58 (20.1)
9–<10	15 (50.0)	34 (36.2)	81 (49.1)	130 (45.0)
10–<11	3 (10.0)	35 (37.2)	40 (24.2)	78 (27.0)
11–<12	1 (3.3)	10 (10.6)	6 (3.6)	17 (5.9)
12–<13	0	1 (1.1)	4 (2.4)	5 (1.7)
≥13	0	1 (1.1)	0	1 (0.3)
Breast cancer
Hemoglobin (g/dL)	Non-metastatic (N=65) (%)	Metastatic (N=21) (%)	Not determined (N=9) (%)	Total (N=95) (%)
≤9	7 (10.8)	6 (30.0)	0	13 (13.8)
9–<10	24 (36.9)	5 (25.0)	5 (55.6)	34 (36.2)
10–<11	27 (41.5)	6 (30.0)	2 (22.2)	35 (37.2)
11–<12	6 (9.2)	3 (15.0)	1 (11.1)	10 (10.6)
12–<13	0	0	1 (11.1)	1 (1.1)
≥13	1 (1.5)	0	0	1 (1.1)

Table 4 Most recently performed blood tests at enrollment

	Mean (SD)	Median (min, max)
Hematocrit (%)
Lymphoma/myeloma (n=29)	28.2 (3.2)	27.4 (23.2, 36.1)
Solid tumors (n=255)	30.1 (3.3)	30.0 (21.0, 44.0)
Breast cancer (n=91)	30.6 (3.3)	30.7 (21.0, 44.0)
Other solid tumors (n=164)	29.8 (3.3)	29.8 (21.4, 41.9)
Total (n=284)	29.9 (3.4)	29.9 (21.0, 44.0)
Reticulocytes (mm^3)
Lymphoma/myeloma (n=4)	18.5 (1.9)	19.0 (16.0, 20.0)
Solid tumors (n=85)	11,357.2 (30,834.9)	35.4 (2.0, 132,000.0)
Breast cancer (n=48)	12,689.9 (33,041.5)	41.3 (5.0, 132,000.0)
Other solid tumors (n=37)	9,628.4 (28,066.8)	33.0 (2.0, 116,000.0)
Total (n=89)	10,847.6 (30,218.4)	34.6 (2.0, 132,000.0)
Serum iron (μg/dL)
Lymphoma/myeloma (n=11)	75.8 (62.6)	54.3 (23.0, 239.0)
Solid tumors (n=78)	70.8 (62.4)	49.9 (12.6, 294.6)
Breast cancer (n=18)	65.5 (52.4)	53.9 (12.6, 243.0)
Other solid tumors (n=60)	72.5 (65.4)	46.6 (15.0, 294.6)
Total (n=89)	71.5 (62.1)	50.9 (12.6, 294.6)
Ferritin (μg/L)
Lymphoma/myeloma (n=12)	787.8 (985.5)	390.3 (20.4, 3,307.4)
Solid tumors (n=150)	554.7 (697.4)	396.5 (15.0, 5,547.0)
Breast cancer (n=61)	623.9 (865.5)	401.0 (39.0, 5,547.0)
Other solid tumors (n=89)	507.3 (554.3)	3,64.0 (15.0, 3,183.0)
Total (n=162)	572.0 (721.3)	396.5 (15.0, 5,547.0)
Transferrin saturation (%)
Lymphoma/myeloma (n=7)	23.2 (22.4)	17.1 (5.0, 70.3)
Solid tumors (n=42)	28.3 (23.6)	21.3 (6.0, 92.9)
Breast cancer (n=7)	19.4 (8.6)	18.5 (8.0, 35.0)
Other solid tumors (n=35)	30.1 (25.2)	22.0 (6.0, 92.9)
Total (n=49)	27.6 (23.2)	21.1 (5.0, 92.9)

Abbreviation: SD, standard deviation.

Table 5 Changes in mean hemoglobin values

Visit	Underlying disease	Mean (SD)	Median (min, max)
Enrollment	Lymphoma/myeloma (n=30)	9.2 (0.9)	9.2 (7.6, 11.7)
	Solid tumors (n=259)	9.8 (1.0)	9.8 (6.9, 13.7)
	Breast cancer (n=94)	10.0 (1.0)	10.1 (6.9, 13.7)
	Other solid tumors (n=165)	9.7 (0.9)	9.7 (7.6, 12.9)
	Total (n=289)	9.7 (1.0)	9.7 (6.9, 13.7)
Follow-up	Lymphoma/myeloma (n=27)	11.0 (1.8)	11.3 (6.2, 14.0)
	Solid tumors (n=223)	11.0 (1.3)	11.0 (7.1, 15.0)
	Breast cancer (n=71)	11.1 (1.2)	11.3 (7.1, 15.0)
	Other solid tumors (n=152)	10.9 (1.4)	11.0 (7.7, 15.0)
	Total (n=250)	11.0 (1.4)	11.1 (6.2, 15.0)
Final	Lymphoma/myeloma (n=17)	11.7 (2.3)	12.3 (5.7, 14.2)
	Solid tumors (n=166)	11.4 (1.4)	11.4 (7.4, 16.0)
	Breast cancer (n=76)	11.7 (1.2)	11.8 (7.7, 16.0)
	Other solid tumors (n=90)	11.1 (1.5)	11.2 (7.4, 14.4)
	Total (n=183)	11.4 (1.5)	11.5 (5.7, 16.0)

Note: Hemoglobin values were only available for 289 patients at enrollment.

Abbreviation: SD, standard deviation.

Table 6 Hemoglobin values by malignancy type

Visit	Hemoglobin (g/dL)	Lymphoma/myeloma (N=30) (%)	Breast cancer (N=95) (%)	Other solid tumors (N=165) (%)	Total* (N=290) (%)
Enrollment	≤9	11 (36.7)	13 (13.8)	34 (20.6)	58 (20.1)
	9–<10	15 (50.0)	34 (36.2)	81 (49.1)	130 (45.0)
	10–<11	3 (10.0)	35 (37.2)	40 (24.2)	78 (27.0)
	11–<12	1 (3.3)	10 (10.6)	6 (3.6)	17 (5.9)
	12–<13	0	1 (1.1)	4 (2.4)	5 (1.7)
	≥13	0	1 (1.1)	0	1 (0.3)
Follow-up	≤9	3 (11.1)	2 (2.8)	13 (8.6)	18 (7.2)
	9–<10	4 (14.8)	7 (9.9)	26 (17.1)	37 (14.8)
	10–<11	5 (18.5)	20 (28.2)	44 (28.9)	69 (27.6)
	11–<12	8 (29.6)	30 (42.3)	42 (27.6)	80 (32.0)
	12–<13	6 (22.2)	9 (12.7)	19 (12.5)	34 (13.6)
	≥13	1 (3.7)	3 (4.2)	8 (5.3)	12 (4.8)
Final	≤9	3 (17.6)	1 (1.3)	8 (8.9)	12 (6.6)
	9–<10	1 (5.9)	5 (6.6)	15 (16.7)	21 (11.5)
	10–<11	0	12 (15.8)	18 (20.0)	30 (16.4)
	11–<12	4 (23.5)	27 (35.5)	24 (26.7)	55 (30.1)
	12–<13	4 (23.5)	23 (30.3)	18 (20.0)	45 (24.6)
	≥13	5 (29.4)	8 (10.5)	7 (7.8)	20 (10.9)

Note:

* Hemoglobin values were only available for 289 patients at enrollment.

Table 7 Responder analysis by criterion

Criterion	Lymphoma/myeloma (N=30) (%)	Breast cancer (N=95) (%)	Other solid tumors (N=165) (%)	Total (N=290) (%)
Criterion 1	13 (43.3)	72 (75.8)	68 (41.2)	153 (52.8)
Criterion 2	19 (63.3)	41 (43.2)	81 (49.1)	141 (48.6)
Criterion 3	19 (63.3)	50 (52.6)	83 (50.3)	152 (52.4)
≥1 Criterion	25 (83.3)	87 (91.6)	134 (81.2)	246 (84.8)

Notes: Criterion 1, hemoglobin ≥10 g/dL after 6 months; Criterion 2, rise in hemoglobin value by 1 g/dL; Criterion 3, individual patient hemoglobin target established at enrollment.

Table 8 Change in hematocrit

Visit	Underlying disease	Mean (SD)	Median (min, max)
Enrollment	Lymphoma/myeloma, n=29	28.2 (3.2)	27.4 (23.2, 36.1)
	Solid tumors, n=255	30.1 (3.3)	30.0 (21.0, 44.0)
	Breast cancer, n=91	30.6 (3.3)	30.7 (21.0, 44.0)
	Other solid tumors, n=164	29.8 (3.3)	29.8 (21.4, 41.9)
	Total, n=284	29.9 (3.4)	29.9 (21.0, 44.0)
Follow-up	Lymphoma/myeloma, n=27	33.6 (5.8)	35.0 (18.7, 42.0)
	Solid tumors, n=217	34.0 (4.2)	34.4 (21.7, 47.8)
	Breast cancer, n=69	34.5 (3.7)	35.1 (22.0, 45.9)
	Other solid tumors, n=148	33.8 (4.4)	34.0 (21.7, 47.8)
	Total, n=244	34.0 (4.4)	34.5 (18.7, 47.8)
Final	Lymphoma/myeloma, n=17	35.2 (6.3)	36.7 (21.5, 42.8)
	Solid tumors, n=164	35.2 (4.3)	35.7 (21.8, 46.2)
	Breast cancer, n=75	36.1 (3.7)	36.2 (24.0, 46.2)
	Other solid tumors, n=89	34.4 (4.6)	35.0 (21.8, 46.1)
	Total, n=181	35.2 (4.5)	35.7 (21.5, 46.2)

Abbreviation: SD, standard deviation.

Table 9 Treatment-emergent adverse events

Adverse event, n (%)	Lymphoma/myeloma (N=30)	Breast cancer (N=95)	Other solid tumors (N=165)	Total (N=290)
At least one adverse event	0	11 (11.6)	14 (8.5)	25 (8.6)
Increase in blood pressure*	0	0	1 (0.6)	1 (0.3)
Influenza-like symptoms*	0	1 (1.1)	3 (1.8)	4 (1.4)
Hemorrhage	0	0	2 (1.2)	2 (0.7)
Upper gastrointestinal bleeding with ulcerative fungal esophagitis	0	0	1 (0.6)	1 (0.3)
Vaginal bleeding	0	0	1 (0.6)	1 (0.3)
Infection	0	5 (5.3)	4 (2.4)	9 (3.1)
Bladder infection, tonsillitis, fever	0	1 (1.1)	0	1 (0.3)
Dyspnea, fever	0	0	1 (0.6)	1 (0.3)
Gangrene	0	0	1 (0.6)	1 (0.3)
Urinary tract infection	0	0	1 (0.6)	1 (0.3)
Mucositis	0	1 (1.1)	0	1 (0.3)
Nail bed inflammation of the toe	0	1 (1.1)	0	1 (0.3)
Pneumonia	0	0	1 (0.6)	1 (0.3)
Port infection	0	1 (1.1)	0	1 (0.3)
Febrile neutropenia	0	1 (1.1)	0	1 (0.3)
Thromboembolic complications	0	3 (3.2)	4 (2.4)	7 (2.4)
Right arm veins	0	1 (1.1)	1 (0.6)	2 (0.7)
Pulmonary artery embolism	0	1 (1.1)	0	1 (0.3)
Pulmonary embolism	0	1 (1.1)	0	1 (0.3)
Pulmonary embolism; deep vein thrombosis	0	0	1 (0.6)	1 (0.3)
Thrombocytopenia	0	0	1 (0.6)	1 (0.3)
Vein thrombosis femolaris left	0	0	1 (0.6)	1 (0.3)
Nonspecific skin rash*	0	3 (3.2)	2 (1.2)	5 (1.7)
Hypersensitivity reactions*	0	1 (1.1)	0	1 (0.3)

Note:

* No description of these events was available.

Table 10 Treatment-emergent serious adverse events

Serious adverse event, n (%)	Lymphoma/myeloma (N=30)	Breast cancer (N=95)	Other solid tumors (N=165)	Total (N=290)
At least one serious adverse event	0	3 (3.2)	5 (3.0)	8 (2.8)
Hemorrhage	0	0	2 (1.2)	2 (0.7)
Upper gastrointestinal bleeding with ulcerative fungal esophagitis	0	0	1 (0.6)	1 (0.3)
Vaginal bleeding	0	0	1 (0.6)	1 (0.3)
Infection	0	1 (1.1)	2 (1.2)	3 (1.0)
Dyspnea, fever	0	0	1 (0.6)	1 (0.3)
Pneumonia	0	0	1 (0.6)	1 (0.3)
Febrile neutropenia	0	1 (1.1)	0	1 (0.3)
Thromboembolic complications	0	2 (2.1)	1 (0.6)	3 (1.0)
Pulmonary artery embolism	0	1 (1.1)	0	1 (0.3)
Pulmonary embolism	0	1 (1.1)	0	1 (0.3)
Pulmonary embolism; deep vein thrombosis	0	0	1 (0.6)	1 (0.3)