Table 4.

Grade ≥3 Adverse Events by Treatment Within the Mutated KRAS Patient Group^a

	No. (%) of Patients
	mFOLFOX6 (n = 367)			mFOLFOX6 + Cetuximab (n = 342)
Adverse Eventsb	Grade 3	Grade 4	Grade 5	Grade 3	Grade 4	Grade 5	P Valuec
Overall	139 (37.9)	64 (17.4)	1 (0.3)	164 (48.0)	78 (22.8)	5 (1.5)	<.001
Hypersensitivity allergy	8 (2.2)	1 (0.3)	0	16 (4.7)	4 (1.2)	0	.02
Cardiovascular
Thrombosis	9 (2.5)	3 (0.8)	0	13 (3.8)	7 (2.0)	0	.10
Infarction	2 (0.5)	1 (0.3)	0	1 (0.3)	2 (0.6)	0	>.99d
Constitutional symptoms
Fatigue	12 (3.3)	1 (0.3)	0	14 (4.1)	3 (0.9)	0	.35
Weight loss	1 (0.3)	0	0	3 (0.9)	0	0	.36d
Acne/rash	0	0	0	69 (20.2)	4 (1.2)	0	<.001d
Gastrointestinal
Diarrhea	27 (7.4)	2 (0.5)	0	51 (14.9)	1 (0.3)	0	.002
Stomatitis/mucositis	10 (2.7)	0	0	19 (5.6)	0	0	.06
Nausea	7 (1.9)	0	0	17 (5.0)	1 (0.3)	0	.02
Vomiting	13 (3.5)	0	0	16 (4.7)	1 (0.3)	0	.35
Anorexia	2 (0.5)	0	0	6 (1.8)	0	0	.16d
Neutropenia	0	43 (11.7)	0	1 (0.3)	45 (13.2)	0	.49
Infection	7 (1.9)	2 (0.5)	0	14 (4.1)	3 (0.9)	1 (0.3)	.05
Febrile neutropenia	0	1 (0.3)	0	6 (1.8)	1 (0.3)	0	.03d
Pneumonia	5 (1.4)	0	0	1 (0.3)	0 (0.0)	0	.22d
Hypomagnesemia	0	0	0	4 (1.2)	2 (0.6)	0	.01d
Paresthesias	68 (18.5)	0	0	46 (13.5)	1 (0.3)	0	.08
Pulmonary
Dyspnea	7 (1.9)	0	0	7 (2.0)	0	0	.89
Pneumonitis	2 (0.5)	0	1 (0.3)	1 (0.3)	1 (0.3)	0	>.99d

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

^aPatients with mutated KRAS treated with mFOLFOX6 having grade 3, grade 4, and grade 5 of any classification was 37.8%, 17.4%, and 0.3%, respectively. Addition of cetuximab for these patients resulted in grade 3, grade 4, and grade 5 toxicity rates of 47.8%, 22.7%, and 1.5%, respectively. During all adverse events experienced, the rate of toxicity of grade 3 or higher was significantly higher for patients with mutated 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.