AUDIENCE: Oncology, Pharmacy, Risk Manager
ISSUE:FDA is alerting health care professionals, oncology clinical investigators, and the public about decreased survival associated with the use of pembrolizumab (Keytruda) or atezolizumab (Tecentriq) as single therapy (monotherapy) in clinical trials to treat patients with metastatic urothelial cancer who have not received prior therapy and who have low expression of the protein programmed death ligand 1 (PD-L1).
In two ongoing clinical trials (KEYNOTE-361 and IMVIGOR-130), the Data Monitoring Committees' (DMC) early reviews found patients in the monotherapy arms of both trials with PD-L1 low status had decreased survival compared to patients who received cisplatin- or carboplatin-based chemotherapy.
Health care professionals should be aware that the populations enrolled in the ongoing clinical trials were eligible for platinum-containing chemotherapy, and therefore differ from those enrolled in the trials that led to the accelerated approvals of both pembrolizumab and atezolizumab in the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
BACKGROUND:Both pembrolizumab and atezolizumab are currently approved under accelerated approval for the treatment of locally advanced or metastatic urothelial carcinoma patients who are not eligible for cisplatin-containing chemotherapy, irrespective of PD-L1 status. Pembrolizumab and atezolizumab are also currently approved by the FDA for the treatment of multiple types of other cancers.
RECOMMENDATION: Patients should talk to their doctor if they have questions or concerns about either drug. Patients taking pembrolizumab or atezolizumab for other approved uses should continue to take their medication as directed by their health care professional.
FDA recommends providers select patients for the treatment of locally advanced or metastatic urothelial cancer using the criteria described in Section 14 of each label. These criteria supported the approvals for pembrolizumab and atezolizumab for initial monotherapy in cisplatin-ineligible patients.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Why is this medication prescribed?
Atezolizumab injection is used to treat urothelial cancer (cancer of the lining of the bladder and other parts of the urinary tract) that has spread to other parts of the body and cannot be removed by surgery or treated with other chemotherapy medications, or has worsened during or after treatment with certain chemotherapy medications. It is also used to treat a certain type of lung cancer (non-small cell lung cancer; NSCLC) that has spread to other parts of the body and has not improved during or after treatment with chemotherapy medications. Atezolizumab injection is in a class of medications called monoclonal antibodies. It works by blocking the action of a certain protein in cancer cells. This helps the person's immune system to fight against the cancer cells, and helps to slow tumor growth.
How should this medicine be used?
Atezolizumab injection comes as liquid to be injected into a vein over 30–60 minutes by a doctor or nurse in a hospital or medical facility. It is usually injected once every 3 weeks. The length of your treatment depends on how well your body responds to the medication and the side effects that you experience.
Atezolizumab injection may cause serious reactions during the infusion of the medication. A doctor or nurse will monitor you carefully while you are receiving the medication. If you experience any of the following symptoms, tell your doctor immediately: flushing, fever, chills, shaking, dizziness, feeling faint, shortness of breath, difficulty breathing, itching, rash, back or neck pain, or swelling of the face.
Your doctor may need to slow down your infusion, delay or stop your treatment, or treat you with other medications if you experience certain side effects. Be sure to tell your doctor how you are feeling during your treatment with atezolizumab.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with atezolizumab injection and each time you receive the medication. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before receiving atezolizumab injection,
- tell your doctor and pharmacist if you are allergic to atezolizumab, any other medications, or any of the ingredients in atezolizumab injection. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you are being treated for an infection. Also tell your doctor if you have or have ever had an organ transplant; lung or breathing problems; disease that affects your nervous system such as myasthenia gravis (a disorder of the nervous system that causes muscle weakness) or Guillain-Barre syndrome (weakness, tingling, and possible paralysis due to sudden nerve damage); autoimmune disease (condition in which the immune system attacks a healthy part of the body) such as Crohn's disease (condition in which the immune system attacks the lining of the digestive tract causing pain, diarrhea, weight loss, and fever), diabetes; ulcerative colitis (condition that causes swelling and sores in the lining of the colon [large intestine] and rectum) or lupus (condition in which the immune system attacks many tissues and organs including the skin, joints, blood, and kidneys); or liver disease.
- tell your doctor if you are pregnant or plan to become pregnant. If you are female, you will need to take a pregnancy test before you receive atezolizumab injection. You should not become pregnant during your treatment and for 5 months after your final dose. Talk to your doctor about birth control methods that you can use during your treatment. If you become pregnant while taking atezolizumab injection, call your doctor immediately.
- tell your doctor if you are breastfeeding. Your doctor may tell you not to breastfeed during your treatment and for 5 months after your final dose.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
If you miss an appointment to receive your medication, call your doctor as soon as possible to reschedule your appointment.
What side effects can this medication cause?
Atezolizumab injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- back, neck, or joint pain
- pale skin
- feeling hot or cold
- swelling of arms
- loss of appetite
- hair loss
- deepening of voice or hoarseness
- weight gain or loss
Some side effects can be serious. If you experience any of these symptoms call your doctor immediately or get emergency medical treatment:
- stomach pain
- stomach bloating or swelling
- severe nausea or vomiting
- bloody or black tarry stools
- decreased urination
- frequent, urgent, or painful urination
- difficulty urinating
- pink, red, or dark brown urine
- swelling in your legs, ankles, or feet
- warm, red, swollen, or tender leg
- new or worsening cough
- coughing up blood
- shortness or breath
- chest pain
- yellowing of the skin or eyes
- bleeding or bruising easily
- pain on right side of stomach area
- extreme tiredness or drowsiness
- headaches that won't go away or unusual headaches
- neck stiffness
- sensitivity to light
- numbness or tingling in your hands, feet, arms, or legs
- muscle weakness
- problems with your vision
- eye pain or redness
- dizziness or feeling faint
- feeling more hungry or thirsty than usual
- changes in mood or behavior (decreased sex drive, irritability, confusion, or forgetfulness)
- sore throat, chills, flu like symptoms, or other signs of infection
- breath that smells fruity
- slowed, fast or irregular heartbeat
Atezolizumab injection may cause other side effects. Call your doctor if you have any unusual problems while receiving this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
In case of emergency/overdose
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests before and during your treatment with atezolizumab injection to check your body's response to the medication.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.