Table 3.
Grade ≥3 Adverse Events by Treatment Within the Wild-Type KRAS Patient Groupa
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.
Patients 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%.
Based 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.
Two-sided χ2 test comparing the rate of grade 3 or higher by treatment.
By Fisher exact test.