Summary: testing, monitoring, and supportive care relevant to lirafugratinib

Care management starts with molecular profiling at initiation of first-line systemic therapy, using a method able to detect FGFR2 fusions with unknown partners, so that an FGFR2 fusion or rearrangement is known before progression. During lirafugratinib therapy, a comprehensive ophthalmological examination including optical coherence tomography of the macula is required before initiation, every 2 months for the first 13 months, and every 4 months thereafter, with urgent evaluation for visual symptoms; retinal pigment epithelial detachment occurred in 31% of recipients (grade 3 in 1.8%) at a median of 57 days, and dry eye in 38%, treated with ocular demulcents. The corresponding schedule for pemigatinib and futibatinib is every 2 months for the first 6 months and every 3 months thereafter. Serum phosphate is monitored throughout treatment; hyperphosphatemia occurred in 21% of lirafugratinib recipients at a median of 15 days, and phosphate binders were required in 7 (1.8%), whereas the pemigatinib and futibatinib labels specify a low-phosphate diet and phosphate-lowering therapy at defined serum thresholds. Effective contraception is required during treatment and for 6 months (females) or 3 months (males with female partners) after the last dose.

Disease-directed care continues alongside targeted therapy: follow-up every 8 to 12 weeks with CT or MRI and CA 19-9 or CEA where secreted, biliary drainage for obstruction, prompt treatment of biliary sepsis, and education on stent patency. Serial circulating tumour DNA can detect emerging resistance mutations before radiologic progression.

Ophthalmologic monitoring for retinal pigment epithelial detachment with lirafugratinib

“Among 385 patients who received LYRFIGTU, RPED occurred in 31% of patients, including Grade 3 events in 1.8%. The median time to first onset was 57 days. RPED led to dose interruption in 15% of patients and dose reduction in 10%.” (opens the source at this quote in a new tab)
“Perform a comprehensive ophthalmological examination, including OCT of the macula, prior to initiation of therapy, every 2 months for the first 13 months, and every 4 months thereafter. For onset of visual symptoms, obtain ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or discontinuation of LYRFIGTU. Withhold, reduce the dose, or discontinue LYRFIGTU based on severity.” (opens the source at this quote in a new tab)
“Dry eye occurred in 38% of patients. Treat patients with ocular demulcents as needed.” (opens the source at this quote in a new tab)

Serum phosphate monitoring with lirafugratinib

“Hyperphosphatemia occurred in 21% of patients. The median time to onset was 15 days. Hyperphosphatemia led to dose interruption in one (0.3%) patient and no permanent discontinuation. Monitor serum phosphate throughout treatment and manage as clinically appropriate.” (opens the source at this quote in a new tab)

Contraception counselling for embryo-fetal toxicity

“Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose.” (opens the source at this quote in a new tab)

Ophthalmologic monitoring and phosphate management with pemigatinib

“Perform a comprehensive ophthalmological examination including OCT prior to initiation of PEMAZYRE and every 2 months for the first 6 months and every 3 months thereafter during treatment.” (opens the source at this quote in a new tab)
“Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is > 5.5 mg/dL. For serum phosphate levels > 7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of hyperphosphatemia” (opens the source at this quote in a new tab)

Ophthalmologic monitoring and phosphate management with futibatinib

“Perform a comprehensive ophthalmological examination, including OCT of the macula, prior to initiation of therapy, every 2 months for the first 6 months, and every 3 months thereafter.” (opens the source at this quote in a new tab)
“Monitor for hyperphosphatemia throughout treatment. Initiate a low phosphate diet and phosphate lowering therapy when serum phosphate level is ≥5.5 mg/dL. For serum phosphate levels >7 mg/dL, initiate or intensify phosphate lowering therapy and dose reduce, withhold, or permanently discontinue LYTGOBI based on duration and severity of hyperphosphatemia” (opens the source at this quote in a new tab)

Longitudinal ctDNA monitoring during FGFR inhibitor therapy

“Examination of serial biopsies, circulating tumor DNA (ctDNA), and patient-derived ICC cells revealed that TAS-120 was active against multiple FGFR2 mutations conferring resistance to BGJ398 or Debio1347.” (opens the source at this quote in a new tab)

“The integration of information from various plasma biomarkers holds the potential to predict clinical outcomes and identify treatment failure prior to radiologic progression, offering valuable guidance for the clinical management of patients with iCCA.” (opens the source at this quote in a new tab)

Follow-up interval and tumor marker monitoring during systemic therapy

“During systemic and locoregional therapy for advanced disease, follow-up should be conducted at a frequency of 8-12 weeks. In addition to imaging with CT or MRI, CA 19-9 or CEA levels may be used to monitor the course of the disease if one or both are known to be secreted [IV, A]” (opens the source at this quote in a new tab)

Biliary drainage, infection management, and patient education

“In patients with biliary obstruction, biliary drainage and subsequent treatment should be carried out; when endoscopic access is not possible, percutaneous transhepatic drainage is recommended [IV, A]” (opens the source at this quote in a new tab)
“Sepsis secondary to biliary obstruction is common and should be treated promptly [IV, A]” (opens the source at this quote in a new tab)
“Patients should be advised of the likely duration of stent patency and of symptoms and signs which are indicative of biliary obstruction or infection [V, A]” (opens the source at this quote in a new tab)

Lirafugratinib (Lyrfigtu)

Care management intervention strategies