Squamous Cell Carcinoma of the Head and Neck, Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Squamous Cell Carcinoma of the Head and Neck Metastatic Colorectal Cancer Head and Neck Cancer

Important Safety Information including Boxed WARNINGS

Allergic Reaction

Severe allergic reactions due to ERBITUX^® (cetuximab) therapy have occurred in 42 of 1373 patients (3%) receiving ERBITUX during clinical studies, resulting in death in less than 1 in 1000 patients
- Symptoms can include trouble with breathing (including tightening of the airways, wheezing, or hoarseness), low blood pressure, shock, loss of consciousness, and/or heart attack
- Approximately 90% of the severe allergic reactions occurred with the first dose of ERBITUX, although some patients experienced their first severe allergic reaction during a subsequent dose of ERBITUX
- Your doctor or nurse should watch you closely for these symptoms during treatment and may need to stop therapy in the event of an allergic reaction
- Severe allergic reactions require that treatment with ERBITUX be stopped immediately and not started again

Heart Attack

Heart attack and/or sudden death occurred in 4 of 208 patients (2%) with head and neck cancer treated with radiation therapy and ERBITUX (cetuximab) as compared to none of 212 patients treated with radiation therapy alone
Heart problems resulting in death and/or sudden death occurred in 7 of 219 patients (3%) with head and neck cancer treated with platinum-based chemotherapy with 5-fluorouracil and cetuximab compared to 4 of 215 patients (2%) treated with chemotherapy alone, based on a study conducted in Europe using European cetuximab
Notify your doctor if you have a history of any heart disease

Lung Disease

Lung disease, which resulted in 1 death, occurred in 4 of 1570 patients (<0.5%) receiving ERBITUX in several clinical trials in colorectal cancer and head and neck cancer
- Notify your doctor if you develop shortness of breath while receiving ERBITUX
- ERBITUX treatment should be stopped if symptoms worsen or lung disease is confirmed

Skin Problems

In several clinical trials in colorectal cancer and head and neck cancer with ERBITUX, skin problems including an acne-like rash, skin drying and cracking, infections (including infections of the blood, skin, eyes, and lips), and abnormal hair growth were seen
- Sun exposure may worsen these effects
- Patients taking ERBITUX should wear sunscreen and hats to limit sun exposure
- A related nail disorder that causes painful swelling of the skin around the nails—most often of the large toes and thumbs—also was reported
- Notify your doctor if you develop any of these symptoms while receiving ERBITUX

ERBITUX Plus Chemotherapy and Radiation

In a controlled study, 940 patients with head and neck cancer received either ERBITUX with radiation therapy and cisplatin (a cancer drug) or radiation therapy and cisplatin alone. Adding ERBITUX resulted in an increase in occurrence of severe or life-threatening redness and sores of the lining of the mouth, lips or throat and other digestive organs; skin reactions caused by certain cancer drugs given after radiation; acne-like rash; heart problems and blood electrolyte disturbances compared to radiation and cisplatin alone
Side effects resulting in death occurred in 20 patients (4.4%) in the ERBITUX treatment arm, and 14 patients (3.0%) in the radiation therapy and cisplatin alone treatment arm
Nine patients in the ERBITUX treatment arm (2.0%) experienced decreased blood flow to the heart compared to 4 patients (0.9%) in the radiation therapy and cisplatin alone treatment arm
The main point of the study was to measure how long patients survived before their cancer got worse. Adding ERBITUX to radiation and cisplatin did not improve this measure

Electrolyte Depletion

Low levels of magnesium and accompanying low calcium and potassium levels have been reported with ERBITUX when given by itself and in combination with other cancer drugs
- Your doctor or nurse should periodically monitor your blood electrolyte levels and administer intravenous replacement as needed

Late Radiation Side Effects

The percentage of late radiation side effects was higher in patients given ERBITUX with radiation therapy compared with patients given radiation therapy alone
- The following sites were affected: organs that produce saliva (65% versus 56%), voice box (52% versus 36%), tissue below the skin (49% versus 45%), lining of the mouth and some organs (48% versus 39%), food pipe (44% versus 35%), and skin (42% versus 33%) in the patients given ERBITUX and radiation versus patients given radiation alone, respectively
The percentage of severe late radiation side effects was similar among patients given radiation therapy alone and patients given ERBITUX plus radiation therapy

Pregnancy and Nursing

Notify your doctor if you are pregnant or if you become pregnant while receiving ERBITUX. Contraception must be used, in both males and females, during ERBITUX therapy and for 6 months following the last dose of ERBITUX. ERBITUX may be passed from the mother to the developing fetus, and may cause harm to the fetus. ERBITUX should only be used during pregnancy if the potential benefit is greater than the potential risk to the fetus
ERBITUX may be passed through human breast milk. Because of the potential for serious side effects in nursing infants from ERBITUX, nursing is not recommended during ERBITUX therapy and for 2 months following the last dose of ERBITUX

Additional Side Effects

In studies of ERBITUX:

The most serious side effects associated with ERBITUX are: allergic reactions, heart attack, skin problems, skin irritation in the radiation area, infection, kidney failure, lung disease, and blood clots in the lung
The most frequent side effects associated with ERBITUX (reported in at least 25% of patients) are skin problems (including rash, itching, and nail changes), headache, diarrhea, and infection

In a study of ERBITUX and radiation therapy given to 208 patients versus radiation therapy alone given to 212 patients with head and neck cancer:

The most frequent side effects were: acne-like rash (87% versus 10%), skin irritation in the radiation area (86% versus 90%), weight loss (84% versus 72%), and feeling weak (56% versus 49%)
Serious side effects reported by at least 10% of patients that received ERBITUX in combination with radiation therapy versus radiation therapy alone included: skin irritation in the radiation area (23% versus 18%), acne-like rash (17% versus 1%), and weight loss (11% versus 7%)

In a study of European cetuximab in combination with platinum-based chemotherapy with 5-fluorouracil given to 219 patients versus chemotherapy alone given to 215 patients with head and neck cancer:

The most frequent side effects were: acne-like rash (70% versus 2%), nausea (54% versus 47%), and infection (44% versus 27%)
Serious side effects reported by at least 10% of patients in either arm were: infection (11% versus 8%)
ERBITUX yields approximately 22% higher blood levels of cetuximab relative to European cetuximab. It is possible that U.S. patients receiving ERBITUX may experience more frequent or severe side effects than patients in the study conducted in Europe

In a study of European cetuximab in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) given to 317 patients versus FOLFIRI alone given to 350 patients with colorectal cancer that had spread to other parts of the body whose tumors had a (KRAS) status known as “wild-type,” as well as a protein called Epidermal Growth Factor Receptor (EGFR):

The most frequent side effects were: acne-like rash (86% versus 13%) and diarrhea (66% versus 60%)
Serious side effects reported by at least 10% of patients in either arm were: abnormal decrease in white blood cell count (31% versus 24%), acne-like rash (18% versus <1%), and diarrhea (16% versus 10%)
ERBITUX yields approximately 22% higher blood levels of cetuximab relative to European cetuximab. In this study, the side effects and severity of adverse reactions seen with European cetuximab were consistent with other studies of U.S. patients receiving ERBITUX for metastatic colorectal cancer

In a study where ERBITUX and supportive care were given to 118 patients versus supportive care which was given to 124 patients with colorectal cancer that had spread to other parts of the body whose tumors had a (KRAS) status known as “wild-type,” as well as a protein called Epidermal Growth Factor Receptor (EGFR):

The most frequent side effects reported were: rash or shedding of the outer layer of the skin (95% versus 21%), feeling tired (91% versus 79%), nausea (64% versus 50%), dry skin (57% versus 15%), other pain (59% versus 37%), and constipation (53% versus 38%)
Serious side effects reported by at least 10% of patients included: fatigue (31% versus 29%), other pain (18% versus 10%), rash or shedding of the outer layer of the skin (16% versus 1%), shortness of breath (16% versus 13%), other intestinal problems (12% versus 5%) and infection without abnormal decrease in white blood cell count (11% versus 5%)

In studies where ERBITUX and irinotecan were given to 354 patients with colorectal cancer that had spread to other parts of the body whose tumors had a protein called Epidermal Growth Factor Receptor (EGFR):

The most frequent side effects reported were: acne-like rash (88%), feeling weakness or discomfort (73%), diarrhea (72%), and nausea (55%)
Serious side effects reported by at least 10% of patients included: diarrhea (22%), decrease in white blood cell count (17%), feeling weakness or discomfort (16%), and acne-like rash (14%)

Please see Important Safety Information and U.S. Complete Product Information including Boxed WARNINGS.

Indications

Head & Neck Cancer:

ERBITUX^® (cetuximab), in combination with radiation therapy, is indicated for the initial treatment of a certain type of locally or regionally advanced head and neck cancer.

ERBITUX, in combination with platinum-based chemotherapy with 5-fluorouracil, is indicated for the initial treatment of patients with a certain type of head and neck cancer whose tumor has returned in the same location or spread to other parts of the body.

ERBITUX is also indicated for use alone to treat patients with a certain type of head and neck cancer whose tumor has returned in the same location or spread to other parts of the body and whose disease has progressed following platinum-based chemotherapy.

Colorectal Cancer:

ERBITUX^® (cetuximab) is approved for the treatment of certain patients who have colorectal cancer that has spread to other parts of the body. Only patients whose tumors have a KRAS mutation-negative gene, commonly known as “wild-type,” and whose tumors have a protein called Epidermal Growth Factor Receptor (EGFR), should receive ERBITUX. FDA-approved tests are used to determine if tumors have these particular traits. Treatment with ERBITUX is given in the following three ways:

In combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for patients who are being treated for this type of cancer for the first time
In combination with another chemotherapy drug, irinotecan, for patients whose disease has progressed after receiving chemotherapy with irinotecan
As a single agent:
- for patients whose disease has progressed after receiving both irinotecan and oxaliplatin
- for patients who are unable to tolerate chemotherapy with irinotecan

ERBITUX is not approved for the treatment of patients whose colorectal cancer tumors are KRAS mutation-positive, or “mutant.”

ERBITUX is available by prescription only.