Patients with advanced bile duct cancer who hope to use the newly approved drug lirafugratinib must first have tumor testing that confirms an FGFR2 gene fusion or rearrangement, and the drug’s label states that no FDA-authorized test for that purpose is available. The FDA approved lirafugratinib, sold as Lyrfigtu, on Sept. 23 for adults whose cholangiocarcinoma was previously treated and cannot be removed by surgery.
That gap puts more responsibility on patients and their oncologists, who must make sure the right test is done. The label also calls for regular eye exams during treatment, because changes in the retina were common in studies.
For families, the practical questions now are about testing, monitoring, and access.
Testing Comes First
Cholangiocarcinoma starts in the bile ducts, which carry bile from the liver to the small intestine. It is rare and often found late, when surgery is no longer possible, because early symptoms are vague or absent. Jaundice, itching, dark urine, pale stools, abdominal pain, fever, and weight loss can appear as the cancer grows, according to the National Cancer Institute.
Only patients whose tumors carry an FGFR2 fusion or other rearrangement qualify for lirafugratinib. These changes are found through comprehensive genomic profiling, usually on a tumor biopsy and sometimes on blood.
According to the prescribing information for Lyrfigtu, FGFR2 status must be confirmed before treatment, but no FDA-authorized test for detecting FGFR2 fusions or rearrangements for this purpose is available. Patients can ask which lab ran their testing, whether it covered FGFR2 fusions and other rearrangements, and whether a new biopsy or blood test is needed.
MedicalDaily previously covered the approval of lirafugratinib. This article focuses on what patients need to do before and during treatment.
Results and Side Effects From the Trial
Approval rested on results from 116 patients in the multicenter, open-label, single-arm REFOCUS trial, according to the FDA. Tumors shrank in 46% of those patients, and responses lasted a median of 11.8 months.
Because the trial had no comparison group, it cannot show whether the drug helps patients live longer than other options. The FDA granted the drug priority review, breakthrough therapy, and orphan drug designations. Elevar Therapeutics markets the drug.
Lirafugratinib is taken by mouth at 70 milligrams once a day. Common side effects include nail problems, skin reactions on the hands and feet, mouth sores, hair loss, dry eye, dry mouth, fatigue, taste changes, constipation, diarrhea, nausea, and decreased appetite.
Eye effects need close attention. Retinal pigment epithelial detachment, a fluid buildup under part of the retina, occurred in 31% of monitored patients, with a median onset of 57 days. The label recommends an eye exam with retinal imaging before starting treatment, every two months for the first 13 months, and every four months after that.
High phosphate levels occurred in 21% of patients, and the drug can harm a developing fetus. Women who can become pregnant should use effective contraception during treatment and for six months after the last dose, and men with partners who can become pregnant should do so for three months.
Steps Patients and Caregivers Can Take
Start by asking the oncologist whether genomic testing has been done and whether it included FGFR2. Other FDA-approved drugs also target FGFR2 changes in bile duct cancer, so test results can open more than one treatment option.
Plan for eye appointments. Patients should ask for a referral to an eye specialist before starting and report blurred vision, eye pain, light sensitivity, or dry, gritty eyes right away.
Report new symptoms promptly. Severe mouth sores, painful skin on the hands or feet, persistent diarrhea, or signs of infection can be managed earlier when caught quickly. Patients should not change their dose without talking to their care team.
Caregivers can help by keeping a simple log of symptoms, eye appointments, and lab results. Bringing that log to each visit makes it easier for the care team to spot side effects early and adjust treatment safely.
Cost and access are real concerns with targeted cancer drugs. Patients can ask about insurance prior authorization, specialty pharmacy coverage, and manufacturer or nonprofit assistance programs. Clinical trials remain an option for many people with bile duct cancer.
Seek urgent care for sudden vision loss, high fever, yellowing skin with fever, severe abdominal pain, or vomiting blood, and call 911 for any life-threatening symptoms.
Questions remain about how lirafugratinib compares with other FGFR2 drugs and whether it extends survival. The drug offers another option for a small group of patients, but only after the right genetic test and with careful eye monitoring throughout treatment.
Key Questions Answered
What is lirafugratinib? A once-daily drug approved Sept. 23 for previously treated advanced bile duct cancer with an FGFR2 fusion or rearrangement.
Who qualifies? Adults whose tumors test positive for an FGFR2 fusion or rearrangement and who have had prior treatment.
Is there an FDA-authorized test? The label says none is available for detecting FGFR2 fusions or rearrangements for this use.
How well did it work? Tumors shrank in 46% of 116 patients, with responses lasting a median of 11.8 months.
What eye monitoring is needed? An eye exam with retinal imaging before treatment, every two months for 13 months, then every four months.
What are common side effects? Nail problems, mouth sores, dry eye, hair loss, fatigue, and digestive symptoms, among others.
Published by Medicaldaily.com