APF530 versus ondansetron, each in a guideline-recommended three-drug regimen, for the prevention of chemotherapy-induced nausea and vomiting due to anthracycline plus cyclophosphamide–based highly emetogenic chemotherapy regimens: a post hoc subgroup analysis of the Phase III randomized MAGIC trial

Figures & data

Figure 1 MAGIC trial AC subgroup CONSORT diagram.

Abbreviations: AC, anthracycline + cyclophosphamide; MAGIC, Modified Absorption of Granisetron In the prevention of CINV; mITT, modified intent-to-treat.

Table 1 Patient demographics and baseline characteristics in patients receiving AC-based regimens (mITT population)

	APF530 500 mg SC arm (n=291)	Ondansetron 0.15 mg/kg IV arm (n=298)
Age, mean (SD), years	54.1 (10.6)	53.8 (10.9)
Female, n (%)	289 (99.3)	293 (98.3)
Ethnicity, n (%)
Not Hispanic/Latino	231 (79.4)	242 (81.2)
Hispanic/Latino/other	60 (20.6)	56 (18.8)
Race, n (%)
White	233 (80.1)	232 (77.9)
Body mass index (kg/m^2)
N	283	290
Mean (SD)	30.3 (6.9)	30.2 (6.9)
ECOG PS, n (%)
0	244 (83.8)	238 (79.9)
1	46 (15.8)	58 (19.5)
Unknown	1 (0.3)	2 (0.7)
Currently drink alcohol, n (%)
Any	111 (38.1)	110 (36.9)
≥8 drinks/week	5 (1.7)	5 (1.7)
Currently smoke tobacco, n (%)	34 (11.7)	34 (11.4)

Abbreviations: AC, anthracycline + cyclophosphamide; ECOG PS, Eastern Cooperative Oncology Group performance status; IV, intravenous; mITT, modified intent-to-treat; SC, subcutaneous; SD, standard deviation.

Table 2 Chemotherapy regimens in patients receiving AC-based regimens (mITT population)

Chemotherapy regimen	Patients, n (%)
	APF530 500 mg SC arm (n=291)	Ondansetron 0.15 mg/kg IV arm (n=298)
Cyclophosphamide (<1500 mg/m^2) + doxorubicin	254 (87.3)	266 (89.3)
Cyclophosphamide (<1500 mg/m^2) + doxorubicin + docetaxel	27 (9.3)	24 (8.1)
Cyclophosphamide (<1500 mg/m^2) + doxorubicin + 5-fluorouracil	5 (1.7)	0
Cyclophosphamide (<1500 mg/m^2) + doxorubicin + rituximab + vincristine	1 (0.3)	3 (1.0)
Cyclophosphamide (<1500 mg/m^2) + doxorubicin + cisplatin (≥50 mg/m^2)	0	2 (0.7)
Cyclophosphamide (<1500 mg/m^2) + doxorubicin + etoposide + rituximab	2 (0.7)	0
Cyclophosphamide (<1500 mg/m^2) + doxorubicin + vincristine	0	2 (0.7)
Cyclophosphamide (<1500 mg/m^2) + doxorubicin + paclitaxel	1 (0.3)	0
Cyclophosphamide (<1500 mg/m^2) + epirubicin	1 (0.3)	0
Cyclophosphamide (≥1500 mg/m^2) + doxorubicin	0	1 (0.3)

Abbreviations: AC, anthracycline + cyclophosphamide; IV, intravenous; mITT, modified intent-to-treat; SC, subcutaneous.

Table 3 Complete response, complete control, and total response during delayed, overall, and acute CINV in patients receiving AC-based regimens (mITT population)

Response and phase, n (%)	APF530 500 mg SC arm (n=291)	Ondansetron 0.15 mg/kg IV arm (n=298)	Treatment difference (95% CI), % (APF530 − ondansetron)	P valuea
Complete response
Delayed	185 (63.6)	167 (56.0)	7.5 (−0.4, 15.4)	0.062
Overall	163 (56.0)	153 (51.3)	4.7 (−3.4, 12.7)	0.256
Acute	205 (70.4)	204 (68.5)	2.0 (−5.4, 9.4)	0.600
Complete control
Delayed	171 (58.8)	156 (52.3)	6.4 (−1.6, 14.4)	0.117
Overall	149 (51.2)	143 (48.0)	3.2 (−4.9, 11.3)	0.435
Acute	193 (66.3)	191 (64.1)	2.2 (−5.5, 9.9)	0.570
Total response
Delayed	119 (40.9)	107 (35.9)	5.0 (−2.9, 12.8)	0.213
Overall	100 (34.4)	94 (31.5)	2.8 (−4.8, 10.4)	0.466
Acute	164 (56.4)	173 (58.1)	−1.7 (−9.7, 6.3)	0.677

Note:

a Based on the chi-square test.

Abbreviations: AC, anthracycline + cyclophosphamide; CI, confidence interval; CINV, chemotherapy-induced nausea and vomiting; IV, intravenous; mITT, modified intent-to-treat; SC, subcutaneous.

Table 4 Patients with no rescue medication use by CINV phases in patients receiving AC-based regimens (mITT population)a

CINV phase	APF530 500 mg SC arm (n=291)	Ondansetron 0.15 mg/kg IV arm (n=298)	Treatment difference (95% CI), % (APF530 − ondansetron)	P valueb
Delayed
nc	289	295
No rescue medication, n (%)	199 (68.9)	182 (61.7)	−7.2 (−14.9, 0.5)	0.069
Overall
nc	289	295
No rescue medication, n (%)	183 (63.3)	168 (56.9)	−6.4 (−14.3, 1.6)	0.116
Acute
nc	291	295
No rescue medication, n (%)	220 (75.6)	211 (71.5)	−4.1 (−11.2, 3.1)	0.263

Notes:

a Results based on observed data without imputation for missing data.

b Based on the chi-square test.

c Patients with a response.

Abbreviations: AC, anthracycline + cyclophosphamide; CI, confidence interval; CINV, chemotherapy-induced nausea and vomiting; IV, intravenous; mITT, modified intent-to-treat; SC, subcutaneous.

Table 5 Patients with no nausea by CINV phases in patients receiving AC-based regimens (mITT population)a

CINV phase	APF530 500 mg SC arm (n=291)	Ondansetron 0.15 mg/kg IV arm (n=298)	Treatment difference (95% CI), % (APF530 − ondansetron)	P valueb
Delayed
c	287	290
No nausea, n (%)	133 (46.3)	118 (40.7)	5.7 (−2.4, 13.7)	0.171
Overall
nc	288	291
No nausea, n (%)	115 (39.9)	105 (36.1)	3.8 (−4.1, 11.7)	0.340
Acute
nc	290	293
No nausea, n (%)	189 (65.2)	197 (67.2)	−2.1 (−9.7, 5.6)	0.598

Notes:

a Results based on observed data without imputation for missing data.

b Based on the chi-square test.

c Patients with a response.

Abbreviations: AC, anthracycline + cyclophosphamide; CI, confidence interval; CINV, chemotherapy-induced nausea and vomiting; IV, intravenous; mITT, modified intent-to-treat; SC, subcutaneous.

Table 6 TEAEs occurring in ≥10% of patients in any arm receiving AC-based regimens (safety population)

Preferred term, n (%)	APF530 500 mg SC arm (n=293)		Ondansetron 0.15 mg/kg IV arm (n=303)
	All grades	Grade≥3	All grades	Grade≥3
TEAEs (excluding injection site reactions)
Fatigue	72 (24.6)	0	88 (29.0)	2 (0.7)
Constipation	72 (24.6)	0	54 (17.8)	0
Nausea	55 (18.8)	2 (0.7)	55 (18.2)	2 (0.7)
Headache	47 (16.0)	3 (1.0)	64 (21.1)	0
Injection site reactionsa
Bruising	143 (48.8)	11 (3.8)	113 (37.3)	18 (5.9)
Pain	96 (32.8)	3 (1.0)	108 (35.6)	3 (1.0)
Erythema	57 (19.5)	2 (0.7)	87 (28.7)	1 (0.3)
Nodule	55 (18.8)	1 (0.3)	28 (9.2)	2 (0.7)
Swelling	30 (10.2)	2 (0.7)	35 (11.6)	0

Note:

a Both treatment arms received the tri(ethylene glycol) poly(orthoester) polymer SC.

Abbreviations: AC, anthracycline + cyclophosphamide; IV, intravenous; SC, subcutaneous; TEAE, treatment-emergent adverse event.