Table 3.

Grade ≥3 Adverse Events by Treatment Within the Wild-Type KRAS Patient Group^a

	No. (%) of Patients
	mFOLFOX6 (n = 894)			mFOLFOX6 + Cetuximab (n = 931)
Adverse Eventsb	Grade 3	Grade 4	Grade 5	Grade 3	Grade 4	Grade 5	P Valuec
Overall	321 (35.9)	132 (14.8)	4 (0.4)	504 (54.1)	168 (18.0)	10 (1.1)	<.001
Hypersensitivity allergy	21 (2.3)	2 (0.2)	0	47 (5.0)	9 (1.0)	0	<.001
Cardiovascular
Thrombosis	18 (2.0)	15 (1.7)	1 (0.1)	19 (2.0)	14 (1.5)	1 (0.1)	.86
Infarction	2 (0.2)	2 (0.2)	1 (0.1)	5 (0.5)	4 (0.4)	0	.32
Constitutional symptoms
Fatigue	38 (4.3)	0	0	58 (6.2)	2 (0.2)	0	.04
Weight loss	1 (0.1)	0	0	7 (0.8)	0	0	.07d
Acne/rash	3 (0.3)	0	0	184 (19.8)	2 (0.2)	0	<.001d
Gastrointestinal
Diarrhea	75 (8.4)	8 (0.9)	0	145 (15.6)	3 (0.3)	0	<.001
Stomatitis/mucositis	16 (1.8)	0	0	59 (6.3)	0	0	<.001
Nausea	32 (3.6)	0	0	40 (4.3)	1 (0.1)	0	.37
Vomiting	25 (2.8)	2 (0.2)	0	29 (3.1)	0	0	.91
Anorexia	9 (1.0)	0	0	25 (2.7)	1 (0.1)	0	.005
Neutropenia	2 (0.2)	87 (9.7)	0	5 (0.5)	105 (11.3)	0	.20
Infection	23 (2.6)	5 (0.6)	0	60 (6.4)	4 (0.4)	4 (0.4)	<.001
Febrile neutropenia	11 (1.2)	0	0	18 (1.9)	5 (0.5)	0	.05
Pneumonia	6 (0.7)	0	0	3 (0.3)	1 (0.1)	1 (0.1)	.71
Hypomagnesemia	2 (0.2)	1 (0.1)	0	16 (1.7)	4 (0.4)	0	<.001d
Paresthesias	135 (15.1)	3 (0.3)	0	130 (14.0)	3 (0.3)	0	.49
Pulmonary
Dyspnea	5 (0.6)	1 (0.1)	0	24 (2.6)	3 (0.3)	0	<.001
Pneumonitis	3 (0.3)	2 (0.2)	0	3 (0.3)	2 (0.2)	1 (0.1)	.81

Abbreviation: mFOLFOX6, the modified sixth version of the leucovorin, fluorouracil, and oxaliplatin regimen.

^aPatients with wild-type KRAS treated with mFOLFOX6 having grade 3, grade 4, and grade 5 of any classification was 35.9%, 14.8%, and 0.4%, respectively. Addition of cetuximab for these patients resulted in grade 3, grade 4, and grade 5 toxicity rates of 54.1%, 18%, and 1.1%, respectively. During all adverse events experienced, the rate of toxicity of grade 3 or higher was significantly higher for patients with wild-type KRAS treated with cetuximab (2-sided χ² test, P<.01). Fisher exact test used with at least 1 of the cells in a 2×2 table was less than 5%.

^bBased on National Cancer Institute, Common Toxicity Criteria, version 3.0.¹¹ Calculated as the maximum severity over all cycles of treatment. Acne/rash includes acne not otherwise specified, rash/desquamation, rash, skin irritation, and rash acneiform. Stomatitis/mucositis includes oral cavity, small bowel, and pharynx. Infection is all infections except pneunomia and febrile neutropenia. Peripheral neuropathy is included in paresthesias.

^cTwo-sided χ² test comparing the rate of grade 3 or higher by treatment.

^dBy Fisher exact test.