Biosimilar filgrastim vs filgrastim: a multicenter nationwide observational bioequivalence study in patients with chemotherapy-induced neutropenia

Figures & data

Table 1 Patient demographics

Patient demographics	Filgrastim 48 MIU (Neupogen^®)	Filgrastim 30 MIU (Neupogen^®)	Biosimilar filgrastim 30 MIU (Leucostim^®)
Gender, n (%)
Females	51 (47.2)	20 (60.6)	114 (50)
Males	57 (52.8)	13 (39.4)	114 (50)
Total	108 (100)	33 (100)	228 (100)
Age (total), years, n (%)
≤50	46 (43)	17 (51.5)	82 (36)
51–64	39 (36.4)	10 (30.3)	92 (40.4)
≥65	21 (20.6)	6 (18.2)	54 (23.6)
Age (females), years, n (%)
≤50	19 (38)	12 (60)	49 (42.9)
51–64	23 (36.4)	6 (30)	45 (39.6)
≥65	8 (20.6)	2 (10)	20 (17.5)
Age (males), years, n (%)
≤50	27 (47.3)	5 (38.4)	33 (28.9)
51–64	16 (28.1)	4 (30.8)	47 (41.2)
≥65	14 (24.6)	4 (30.8)	34 (29.9)
Weight, kg, n (%)
≤70	32 (20.3)	16 (10.1)	110 (69.6)
≥71	30 (32.3)	5 (5.4)	58 (62.4)
Total	62 (24.7)	21 (8.4)	168 (66.9)

Table 2 Blood counts at baseline

Blood counts	Average
Hematocrit (%)
Females (n=150)	30.1
Males (n=154)	31.8
RBC (10^6/µL)
Females (n=165)	3.5
Males (n=161)	3.66
WBC (10^3/µL)
Females (n=181)	1.82
Males (n=182)	1.86
PLT (10^3/µL)
Females (n=180)	174.3
Males (n=177)	152.3
Neutrophils (10^3/µL)
Females (n=183)	1.14
Males (n=179)	0.48

Abbreviations: RBC, red blood cells; WBC, white blood cells; PLT, platelets.

Table 3 Cancer types in enrolled patients

Cancer type	n	%	Cancer type	n	%
Breast	59	17.5	Bladder	2	0.6
Lung	58	17.1	Neuroendocrine	1	0.3
Colorectal	46	13.6	Brain	2	0.6
Urogenital cancersa	43	12.7	Primary unknown	1	0.3
Head and neckb	12	3.5	Malignant melanoma	2	0.6
Liverc	11	3.3	Medulloblastoma	1	0.3
Lymphomasd	36	10.5	Adenoid cystic carcinoma	1	0.3
Gastric	41	12.1	Adenocarcinomasf	4	1.2
Neuroectodermal	1	0.3	Renal cell carcinoma	1	0.3
Mesenchymal	2	0.6	Parotid carcinoma	1	0.3
Sarcomase	18	5.3	Pancreatic	7	2.07

Notes:

a Urogenital cancers include cervical (n=4), ovarian (n=16), testicular (n=14), seminoma (n=4), endometrial (n=2), germ cell tumor (n=2), and uterus (n=1) cancers.

b Head and neck includes esophageal (n=3), larynx (n=2), nasopharynx (n=2), and tongue (n=1) cancers.

c Liver includes hepatocellular carcinomas (n=4) and hepatoblastoma (n=1).

d Lymphomas include lymphoma (n=11), NH lymphoma (n=15), and Hodgkin lymphoma (n=10).

e Sarcomas include Ewing’s sarcoma (n=2), leiomyosarcoma (n=1), Kaposi’s sarcoma (n=2), fibrosarcoma (n=1), liposarcoma (n=1), mezenchymal (n=2), osteosarcoma (n=4), synovial (n=1), soft tissue sarcoma (n=1), and uterus myosarcoma (n=3).

f Adenocarcinomas include adenocarcinoma (n=1), duodenal (n=1), prostatic (n=1), and gallbladder (n=1).

Abbreviation: NH, non-Hodgkin’s.

Table 4 Chemotherapy courses administered to patients enrolled

Chemotherapeutic agents	A	B	C	D	E	Total	%a
Adriablastin	1	3	–	–	–	4	0.6
Bleomycin	6	9	1	–	–	16	2.2
Carboplatin	12	8	3	–	1	24	3.3
Cisplatin	57	31	8	–	–	96	13.3
Dacarbazine	1	–	–	7	–	8	1.1
Dexamethasone	4	1	6	–	–	11	1.5
Doxorubicin	13	30	12	2	3	60	8.3
Docetaxel	27	12	1	–	–	40	5.5
Epirubicin	4	6	3	–	–	13	1.8
Etoposide	2	33	7	2	–	44	6.1
Fluorouracil	52	23	30	1	–	106	14.6
Folinic acid	10	6	–	3	–	19	2.6
Gemcitabine	11	10	–	–	–	21	2.9
Ifosfamide	12	2	–	1	–	15	2.1
Irinotecan	12	2	2	1	–	17	2.3
Capecitabine	3	5	3	–	–	11	1.5
Methotrexate	1	–	–	–	–	1	0.1
Oxaliplatin	8	4	3	–	–	15	2.1
Paclitaxel	13	7	1	1	–	22	3.0
Pemetrexed	2	–	–	–	–	2	0.3
Cyclophosphamide	14	20	10	2	–	46	6.4
Cytarabin	–	3	–	–	–	3	0.4
Tamoxifen	2	–	–	–	–	2	0.3
UFT (tegafur/uracil)	1	–		–	–	1	0.1
Temozolomide	1	–		–	–	1	0.1
Topotecan	–	–	1	–	–	1	0.1
Trastuzumab	4	5	1	–	–	10	1.4
Vinblastine	–	–	7	–	–	7	1.0
Vincristine	4	3	10	12	–	29	4.0
Vinorelbine	2	6	–	–	–	8	1.1
Zoledronic acid	1	–	2	–	1	4	0.6
Total	337	337	337	337	337	724	100.0

Notes: Definition of capital letters is as follows: A, one course of therapy; B, two courses of therapy; C, three courses of therapy; D, four courses of therapy; and E, five courses of therapy.

a Percentage of column.

Table 5 Allocation of chemotherapy courses per number of patients during the entire study

Number of courses	n	%
Patients received one course of therapy	41	13.7
Patients received two courses of therapy	136	45.5
Patients received three courses of therapy	82	27.4
Patients received four courses of therapy	34	11.4
Patients received five courses of therapy	6	2.0
Total	299	100.0

Table 6 Medications given for the treatment of neutropenia

Medication	n	%
Filgrastim 30 MIU	30	8.9
Biosimilar filgrastim 30 MIU	208	61.9
Filgrastim 48 MIU	98	29.2
Total	336	100.0

Table 7 Percentage of patients recovered from neutropenia within ≤4 days and the percentage of those recovered from neutropenia within ≥5 days

Medication	Time to ANC recovery (days)
	≥5 days, n (%)	≤4 days, n (%)	Total
Filgrastim 30 MIU	13 (43.3)	17 (56.7)	30
Biosimilar filgrastim 30 MIU	79 (39.9)	119 (60.1)	198
Filgrastim 48 MIU	46 (47.4)	51 (52.6)	97
Total	138 (42.5)	187 (57.5)	325

Note: Compared using the chi-square test.

Abbreviation: ANC, absolute neutrophil count.

Table 8 Time to ANC recovery

Medication	Mean ± SD	Median (min–max)
Filgrastim 30 MIU	5.66±4.83	3.5 (2–21)
Biosimilar filgrastim 30 MIU	5.41±4.54	4 (1–21)
Filgrastim 48 MIU	5.63±4.32	4 (1–21)

Note: Compared using Kruskal–Wallis one-way analysis of variance.

Abbreviations: ANC, absolute neutrophil count; SD, standard deviation; min, minimum; max, maximum.

Table 9 Time to ANC recovery in hospitalized patients

Medication	Mean ± SD	Median (min–max)
Filgrastim 30 MIU	3.70±2.18	3 (1–12)
Biosimilar filgrastim 30 MIU	5.09±5.78	2 (2–21)
Filgrastim 48 MIU	5.70±4.20	5 (1–21)

Note: Compared using Kruskal–Wallis one-way analysis of variance.

Abbreviations: ANC, absolute neutrophil count; SD, standard deviation; min, minimum; max, maximum.

Table 10 Duration of neutropenia in patients ≤70 kg

Medication	Duration of neutropenia, mean ± SD, median (min–max)
Biosimilar filgrastim 30 MIU	5.62±4.63, 4 (1–21)
Filgrastim 30 MIU	6.00±5.75, 3 (2–21)
Filgrastim 48 MIU	5.67±3.75, 5 (2–21)

Note: Compared using the Kruskal–Wallis test.

Abbreviations: SD, standard deviation; min, minimum; max, maximum.