Pivotal trial safety
Incidence of adverse events in the randomized, controlled study occurring in >5% of patients with a between group difference of >5% (Vectibix® plus BSC, n=229; BSC, n=234).*
|
|
Vectibix® + BSC |
Vectibix® + BSC |
BSC |
BSC |
|
Body as a Whole |
| |||
|
Fatigue |
26 |
4 |
15 |
3 |
|
General Deterioration |
11 |
8 |
4 |
3 |
|
Digestive |
| |||
|
Abdominal Pain |
25 |
7 |
17 |
5 |
|
Nausea |
23 |
1 |
16 |
< 1 |
|
Diarrhea |
21 |
2 |
11 |
0 |
|
Constipation |
21 |
3 |
9 |
1 |
|
Vomiting |
19 |
2 |
12 |
1 |
|
Stomatitis |
7 |
0 |
1 |
0 |
|
Mucosal Inflammation |
6 |
< 1 |
1 |
0 |
|
Metabolic/Nutritional |
| |||
|
Peripheral Edema |
12 |
1 |
6 |
< 1 |
|
Hypomagnesemia (Lab) |
39 |
4 |
2 |
0 |
|
Respiratory |
|
|
|
|
|
Cough |
14 |
< 1 |
7 |
0 |
|
Skin/Appendages |
| |||
|
All Skin/Integument Toxicity |
90 |
16 |
9 |
0 |
|
Skin |
90 |
14 |
6 |
0 |
|
Erythema |
65 |
5 |
1 |
0 |
|
Acneiform Dermatitis |
57 |
7 |
1 |
0 |
|
Pruritus |
57 |
2 |
2 |
0 |
|
Skin Exfoliation |
25 |
2 |
0 |
0 |
|
Rash |
22 |
1 |
1 |
0 |
|
Skin Fissures |
20 |
1 |
< 1 |
0 |
|
Dry Skin |
10 |
0 |
0 |
0 |
|
Acne |
13 |
1 |
0 |
0 |
|
Nail |
29 |
2 |
0 |
0 |
|
Paronychia |
25 |
2 |
0 |
0 |
|
Other Nail Disorder |
9 |
0 |
0 |
0 |
|
Hair |
9 |
0 |
1 |
0 |
|
Growth of Eyelashes |
6 |
0 |
0 |
0 |
|
Eye |
15 |
< 1 |
2 |
0 |
|
*Version 2.0 of the NCI-CTC was used for grading toxicities. Skin toxicity was coded based on a modification of the NCI-CTCAE, version 3.0. | ||||
_______________________________________________
Indication
Vectibix® (panitumumab) is indicated as a single agent for the treatment of epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma (mCRC) with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
The effectiveness of Vectibix® as a single agent for the treatment of EGFR-expressing mCRC is based on progression-free survival. Currently, no data demonstrate an improvement in disease-related symptoms or increased survival with Vectibix®.
Retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for Vectibix® in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Vectibix® is not recommended for the treatment of colorectal cancer with these mutations.
Important Safety Information, including Boxed WARNINGS
|
WARNING: DERMATOLOGIC TOXICITY and INFUSION REACTIONS Dermatologic Toxicity: Dermatologic toxicities occurred in 89% of patients and were severe (NCI-CTC grade 3 or higher) in 12% of patients receiving Vectibix® monotherapy. [See Product Labeling: Dosage and Administration (2.1), Warnings and Precautions (5.1), and Adverse Reactions (6.1)]. Infusion Reactions: Severe infusion reactions occurred in approximately 1% of patients. [See Product Labeling: Warnings and Precautions (5.2) and Adverse Reactions (6.1)]. Although not reported with Vectibix®, fatal infusion reactions have occurred with other monoclonal antibody products. [See Product Labeling: Dosage and Administration (2.1)]. |
Vectibix® is not indicated for use in combination with chemotherapy. In an interim analysis of a randomized clinical trial, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased overall survival and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix®-treated patients included rash/dermatitis/acneiform (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%) and hypomagnesemia (4% vs 0%). NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix®-treated patients (7% vs 4%) and included fatal events in 3 (< 1%) Vectibix®-treated patients.
In a single-arm study of 19 patients receiving Vectibix® in combination with IFL, the incidence of NCI-CTC grade 3-4 diarrhea was 58%; in addition, grade 5 diarrhea occurred in 1 patient. In a single-arm study of 24 patients receiving Vectibix® plus FOLFIRI, the incidence of NCI-CTC grade 3 diarrhea was 25%.
Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix®. Of the 2 cases, 1 involved a patient with underlying idiopathic pulmonary fibrosis and resulted in death. The second patient had symptoms of pulmonary fibrosis, which was confirmed by CT. Additionally, a third patient died with bilateral pulmonary infiltrates of uncertain etiology with hypoxia.
In the randomized, controlled clinical trial, median magnesium levels decreased by 0.1 mmol/L in the Vectibix® arm; hypomagnesemia (NCI-CTC grade 3 or 4) requiring oral or IV electrolyte repletion occurred in 2% of patients. Patients’ electrolytes should be periodically monitored during and for 8 weeks after the completion of Vectibix® therapy.
Exposure to sunlight can exacerbate dermatologic toxicity. It is recommended that patients wear sunscreen and hats, and limit sun exposure while receiving Vectibix®.
The most common adverse events of Vectibix® are skin rash with variable presentations, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea, including diarrhea resulting in dehydration. The most serious adverse events of Vectibix® are pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, and constipation.
