Patients with advanced bile duct cancer, or cholangiocarcinoma (CCA), have few treatment options and a generally poor prognosis. But now, a new medication called Pemazyre (pemigatinib) has been approved by the Food and Drug Administration (FDA) for the treatment of CCA that has spread to other parts of the body or that cannot be removed by surgery, providing a new treatment option for these patients, and perhaps a better outlook for their future.
This drug should only be used in adults who have already received some treatment for their cancer and whose tumors test positive for an abnormal gene called fibroblast growth factor receptor 2, or FGFR2. Pemazyre is the first targeted therapy to be approved by the FDA for people with advanced CCA and an abnormal FGFR2 gene, so people with advanced CCA should always be tested for an abnormal FGFR2 gene before treatment, because only this particular group of patients are likely to benefit from the drug.
What Is CCA?
CCA starts in the bile ducts, which connect the liver and gallbladder to the small intestine. This type of cancer affects between 2,000 and 3,000 people in the United States each year and occurs more often in men and in people older than 65 years.
About 10% of CCA is intrahepatic (referring to the location of the cancer in relation to the liver), and abnormal FGFR2 genes occur almost entirely in intrahepatic CCA (as opposed to extrahepatic CCA). Altered FGFR2 genes can encourage the growth and survival of cancer cells, so targeting this abnormal gene with a drug like Pemazyre can stop those cancer cells from growing and spreading.
Because people with CCA typically have no symptoms in the early stages of their cancer, the disease is often not found until it is more advanced and harder to treat. When it is in the later stages, it usually cannot be removed by surgery, and treatment options are limited. But now, patients with abnormal FGFR2 genes have another treatment option: Pemazyre.
How to Take Pemazyre
Before taking Pemazyre, patients should tell their doctor about any medical conditions, including any vision or eye problems, or difficulty swallowing tablets. Women who are pregnant or plan to become pregnant should not take this drug as it can cause harm to an unborn baby or result in a miscarriage. Females who can become pregnant and males with female partners who can become pregnant should always use effective birth control when taking this drug, and for 1 week after their final dose. The same rules apply to breastfeeding: patients should not breastfeed during treatment and for 1 week after the final dose. Patients should also tell their healthcare provider about any prescription and over-the-counter medicines they take, including vitamins and herbal supplements.
This drug is available as a tablet and should be taken in cycles of 21 days: once a day (at about the same time each day) for 14 days, followed by 7 days off treatment. It can be taken with or without food, but tablets should be swallowed whole and not crushed, chewed, split, or dissolved. Patients should not consume food or drinks containing grapefruit when taking this drug, because grapefruit is considered a CYP3A inhibitor and might increase the risk of side effects. Other drugs that are strong inhibitors of CYP3A (like clarithromycin or erythromycin) might also increase the risk of side effects with Pemazyre, whereas CYP3A inducers (like rifampicin or St. John’s wort) might make the drug less effective.
If a dose is missed, it can be taken within 4 hours on the same day of the missed dose, but if more than 4 hours have passed (or if taking the tablet led to vomiting), patients should skip that dose and resume regular dosing again the next day at the usual time. Patients should not take more of this medicine than they have been prescribed, even if attempting to make up for missed doses.
The doctor might change the dose or completely stop treatment with Pemazyre if the cancer progresses, or if certain side effects occur. Serious side effects include eye problems (dry eye or inflamed eyes, inflamed cornea [the front part of the eye], increased tears or a disorder of the retina [inside the eye]). To avoid these eye problems, patients will need to see an eye specialist for a complete eye exam before beginning treatment, then again every 2 months for the first 6 months of treatment, and every 3 months during treatment. Using artificial tears or lubricating eye gels can help with dry eye, but patients should tell their healthcare provider right away if any vision changes occur during treatment, including blurred vision or seeing flashes of light or black spots.
Another common but potentially serious side effect of Pemazyre is high phosphate levels in the blood, also called hyperphosphatemia. Patients should have their blood phosphate levels checked during treatment and should tell their doctor right away if they develop any muscle cramps or numbness or tingling around the mouth, as this can be a sign of hyperphosphatemia. If these symptoms occur, providers might prescribe dietary changes or phosphate-lowering therapy, or change, interrupt, or stop treatment if necessary.
In addition to these side effects, other common side effects of Pemazyre include hair loss, diarrhea, nails separating from the bed or poor formation of the nail, feeling tired, change in sense of taste, nausea, constipation, mouth sores, dry mouth, decrease in appetite, vomiting, joint pain, stomach pain, low phosphate in blood, back pain, and dry skin.
However, it’s important to note that these are not all of the possible side effects of Pemazyre, and patients using this drug should call their doctor with any and all concerns.
The approval of Pemazyre is an important advance in the second-line treatment of cholangiocarcinomas harboring genetic alterations in the FGFR pathway. This drug offers new hope to patients who have tumor deposits after having received previous therapy for these aggressive cancers.