Targeted therapies in the treatment of GIST: Adverse events and maximising the benefits of sunitinib through proactive therapy management

Figures & data

Table I. Most common (>15%) treatment-related adverse events associated with sunitinib versus placebo therapy in patients with advanced imatinib-refractory gastrointestinal stromal tumours [22].

Adverse event	Blinded phase				Open-label phase		Blinded + open-label phases
	Sunitinib (n = 235)		Placebo (n = 115)		All patients^‡ (n = 247)		Sunitinib^§ (n =241)
	Grade 1/2 n (%)	Grade 3/4 n (%)	Grade 1/2 n (%)	Grade 3/4 n (%)	Grade 1/2 n (%)	Grade 3/4 n (%)	Grade 1/2 n (%)	Grade 3/4 n (%)
Fatigue	71 (30)	19 (8)	24 (21)	2 (2)	97 (39)	25 (10)	88 (37)	25 (10)
Diarrhoea	73 (31)	8 (3)	9 (8)	0 (0)	77 (31)	11 (4)	92 (38)	12 (5)
Nausea	63 (27)	3 (1)	14 (12)	2 (2)	71 (29)	9 (4)	82 (34)	6 (2)
Anorexia	47 (20)	0 (0)	5 (4)	1 (1)	55 (22)	6 (2)	64 (27)	2 (1)
Dysgeusia	50 (21)	0 (0)	3 (3)	0 (0)	54 (22)	1 (0.4)	60 (25)	1 (0.4)
Vomiting	39 (17)	1 (0.4)	7 (6)	1 (1)	43 (17)	5 (2)	51 (21)	3 (1)
Yellow skin	42 (18)	0 (0)	5 (4)	0 (0)	51 (21)	0 (0)	49 (20)	0 (0)
Mucosal inflammation	34 (14)	2 (1)	0 (0)	0 (0)	40 (16)	5 (2)	44 (18)	4 (2)
Hypertension	21 (9)	11 (5)	5 (4)	1 (1)	36 (15)	19 (8)	29 (12)	18 (7)
Rash	35 (15)	2 (1)	6 (5)	0 (0)	36 (15)	1 (0.4)	43 (18)	3 (1)
Stomatitis	36 (15)	1 (0.4)	1 (1)	0 (0)	35 (14)	4 (2)	42 (17)	3 (1)
Dyspepsia	34 (14)	1 (0.4)	1 (1)	0 (0)	42 (17)	2 (1)	43 (18)	1 (0.1)
Headache	24 (10)	1 (0.4)	7 (6)	0 (0)	43 (17)	3 (1)	41 (17)	3 (1)
Hand-foot syndrome	19 (8)	9 (4)	1 (1)	0 (0)	44 (18)	13 (5)	30 (12)	14 (6)
Asthenia	28 (12)	6 (3)	2 (2)	2 (2)	28 (11)	12 (5)	30 (12)	13 (5)
Hair colour changes	20 (9)	0 (0)	2 (2)	0 (0)	49 (20)	0 (0)	37 (15)	0 (0)
Laboratory abnormalities
Haemoglobin	125 (53)	9 (4)	60 (52)	2 (2)	71 (29)	4 (2)	132 (55)	11 (5)
Neutrophils	106 (45)	24 (10)	4 (3)	0 (0)	58 (23)	16 (6)	113 (47)	28 (12)
Platelets	86 (37)	9 (4)	3 (3)	0 (0)	46 (19)	3 (1)	90 (37)	10 (4)

*Based on the sunitinib arm over the entire study;

^†per-protocol population;

^‡treatment=sunitinib;

§five grade 5 events deemed to be treatment-related occurred in this group (hepatic failure, left ventricular failure, cardiac arrest, cerebral ischaemia, and multi-organ failure).

Table IIa. Comparison of toxicities associated with imatinib therapy at doses of 400 mg/day and 800 mg/day in patients with advanced gastrointestinal stromal tumours in the a) North American phase III study.

Adverse event, n (%)	Imatinib 400 mg/day (n=344)	Imatinib 800 mg/day (n=347)
Blood/bone marrow	68 (20)	92 (27)
Cardiovascular	23 (7)	48 (14)
Constitutional symptoms	14 (4)	30 (9)
Dermatology/skin	14 (4)	26 (7)
Gastrointestinal	31 (9)	54 (16)
Haemorrhagic	18 (5)	38 (11)
Hepatic	12 (3)	13 (4)
Infection/febrile	15 (4)	23 (7)
Pain	37 (11)	42 (12)

Table IIb. Comparison of toxicities associated with imatinib therapy at doses of 400 mg/day and 800 mg/day in patients with advanced gastrointestinal stromal tumours in the b) Euro-Australasian study (Adapted from reference [13]).

Adverse event, n (%)	Imatinib 400 mg/day (n=470)	Imatinib 800 mg/day (n=472)	P-value^a
Oedema	336 (71)	412 (87)	<0.0001
Anaemia	418 (89)	468 (98)	<0.0001
Rash	125 (27)	220 (47)	<0.0001
Nausea	229 (49)	286 (61)	<0.0001
Bleeding	51 (11)	105 (22)	<0.0001
Diarrhoea	226 (48)	268 (57)	0.0026
Dyspnoea	54 (11)	83 (18)	0.036
Pleuritic pain	240 (51)	160 (55)	0.053

^aadjusted for reptitive testing (Hommel Stet-up Procedure).

Table III. Dose reduction/interruptions due to adverse events associated with imatinib therapy at doses of 400 mg/day and 800 mg/day in patients with advanced gastrointestinal stromal tumours.

	Euro Australasian study [14]		North American study [13]
	Imatinib 400 mg/day (n=473)	Imatinib 800 mg/day (n=473)	Imatinib 400 mg/day (n=330)	Imatinib 800 mg/day (n=333)
Dose reductions, n (%)	77 (16)	282 (60)
Due to toxic effects, n (%)	60 (12)	213 (46)	52 (16)	192 (58)
Dose interruptions, n (%)	189 (40)	302 (64)
Due to toxic effects, n (%)	135 (29)	235 (50)	124 (38)	198 (59)

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