What is Crizotinib (Xalkori)? How it Works, Side Effects and More
Crizotinib, also known as Xalkori, is a targeted therapy medication prescribed to many patients with ROS1+ cancer. It can be a very effective treatment and relatively tolerable, as cancer treatments go. The following describes the history of crizotinib, its designation as a first-line ROS1+ NSCLC, side effects and more.
What is Crizotinib (Xalkori)?
According to the Xalkori website, crizotinib is “a prescription medicine used to treat people with non-small cell lung cancer (NSCLC) that has spread to other parts of the body and is caused by a defect in either a gene called ALK (anaplastic lymphoma kinase) or a gene called ROS1.” It has FDA approval for other indications as well.
Clinical trials demonstrated crizotinib effectively treats ALK+ or ROS1+ NSCLC that has spread to other parts of the body (metastatic). Patients were treated with crizotinib at the standard oral dose of 250 mg twice daily and assessed for safety, pharmacokinetics, and response to therapy.
The Objective Response Rate (ORR) measures tumor response to treatment, including tumor shrinkage. The results showed that the ORR of patients taking crizotinib was 72%, meaning 72% of patients saw their tumors shrink significantly.
Crizotinib was approved by the FDA for ROS1+ NSCLC in 2016 and has since been approved in many countries around the world.
How does it treat ROS1+ NSCLC?
Crizotinib enters every cell in the body. In normal cells in the adult body, this has little effect, since ROS1 proteins are usually not expressed in adults. In ROS1+ cancer cells, however, the drug binds to the active ROS1 protein. This inhibits the protein's ability to signal; the cell stops behaving like cancer and can undergo apoptosis (die).
Crizotinib does not treat the brain effectively, but many ROS1ders who were treated first-line with crizotinib have thrived for years with no brain metastases and good quality of life; some even achieved and maintained no evidence of disease. Crizotinib is often less toxic than entrectinib and is approved in more countries than the other ROS1 targeted therapies.
Crizotinib cannot kill 100% of the cancer cells. While crizotinib therapy may control and shrink the cancer, crizotinib cannot cure cancer.
How to take Crizotinib?
Xalkori is manufactured by Pfizer and is the brand name for crizotinib. Xalkori is a pill you take twice a day. Patients must continue to take crizotinib to inhibit the cancer. If the drug is stopped, the cancer is no longer inhibited, and the cancer may resume growing.
Most ROS1 Clinician-Researchers believe patients on ROS1 oral targeted therapies such as crizotinib should not take “drug holidays" (a break from taking their oral cancer drug) if the drug is effective and the patient is tolerating the drug well.
Crizotinib remains in your system for several days, so patients whose doctors advise them to stop taking it for a few days (e.g., before and after a surgery) rarely experience progression.
However, if you stop taking your TKI for longer, your cancer is no longer inhibited and may begin growing again.
An informal survey of patients active in our ROS1der community shows that more than ⅓ currently take Xalkori. Of those patients, about ⅓ have been on the drug for more than four years, approximately ¼ have been on it more than five years, and another almost ⅕ have been on it more than six years. A small handful have even been on Xalkori for 10 years!
Among the current patients in our community who stopped Xalkori, almost half did so due to progression in the brain, and most of the rest did so due to progression elsewhere in the body. Only a small minority stopped Xalkori due to side effects or other issues with their ability to tolerate the drug.
What are the Side Effects of Crizotinib?
According to the Xalkori.com website:
“The most common side effects of Xalkori include: vision problems, nausea, diarrhea, vomiting, swelling of your hands, feet, face and eyes, constipation, increased liver function blood test results, tiredness, decreased appetite, upper respiratory infection, dizziness, feeling of numbness or tingling in the extremities.”
In addition to the common side effects listed on the Xalkori.com website, patients in the ROS1+ Cancer Facebook Group have reported other side effects, including:
Low blood pressure
Low heart rate
Low protein levels
Low iron levels
Elevated creatinine levels
(Note: Additional side effects may also exist. This list is not meant to be exhaustive. Please check the drug labeling and with your doctor for a complete list.)
How Common Are the Side Effects of Crizotinib?
Some people have no side effects, while others have a lot. Patient experiences vary. In general, many patients in the ROS1+ Cancer Facebook Group noticed that side effects like nausea and visual disturbances occurred most strongly in the first few months on the drug, and then waned as their body adjusted. Some patients lucky enough to be on the drug for several years have noticed certain side effects, like edema, increase as the cumulative effect builds up.
To learn more about coping with side effects of crizotinib, please visit our Coping with Side Effects page.
Crizotinib & Allen Fremont: He's a 1der
Research made a big difference when it brought Xalkori to ROS1 cancer patients. So did patients like Allen Fremont.
Allen was diagnosed with lung cancer in 2010 at age 47. Chemotherapy had limited success treating his cancer, but then his cancer was tested for ROS1 at Massachusetts General Hospital. In early 2011 he became the second ROS1+ cancer patient in the world enrolled in the crizotinib trial.
His rapid improvement helped persuade clinical researchers to expand trial enrollment to other ROS1+ cancer patients. His remarkable PET scan images (taken before crizotinib and again seven weeks after starting the drug) were published in the 2014 New England Journal of Medicine article that described results of the initial 50 ROS1+ cancer patients treated with crizotinib. The dramatic improvement shown in his scans helped expedite FDA approval.
Allen continued to benefit from crizotinib for five years before his cancer again progressed. After volunteering for two more targeted therapy clinical trials and receiving additional treatments, Allen died in 2020. As ROS1+ cancer patients look to new research, we celebrate Allen and all those who helped bring Xalkori and other new therapies to our community.