When the U.S. Food and Drug Administration (FDA) granted pemigatinib (Pemazyre®) a new indication in August 2022, it became the first targeted therapy approved for treatment of patients with relapsed or refractory myeloid or lymphoid neoplasms (MLNs) with fibroblast growth factor receptor (FGFR) 1 rearrangement. In 2021, FDA gave pemigatinib accelerated approval for patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement as detected by an FDA-approved test.
Oral targeted agent, small molecule kinase inhibitor targeting FGFR1, FGFR2, FGFR3, and FGFR4
Mechanism of Action
Pemigatinib inhibits phosphorylation and signaling, which prevents tumor cell proliferation and survival in FGFR-driven tumors.
- Treatment of adults with relapsed or refractory MLNs with FGFR1 rearrangement
- Treatment of adult patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement (This indication received accelerated approval based on overall response rate and duration of response.)
- MLNs: Give 13.5 mg orally daily until patients experience disease progression or unacceptable toxicity.
- Cholangiocarcinoma: Give 13.5 mg orally daily for 14 consecutive days followed by 7 days off therapy in 21-day cycles until patients experience disease progression or unacceptable toxicity.
- Severe renal or hepatic impairment: Give 9 mg orally daily for both continuous and intermittent scheduling.
Take by mouth with or without food at the same time each day. Swallow the tablets whole; do not crush, chew, split or dissolve tablets. If you miss a dose by more than four hours or vomit a dose, do not take an extra dose; rather, wait and resume your dosing at the next scheduled time.
The package insert contains warnings and precautions for hyperphosphatemia (which can lead to soft tissue mineralization), embryo-fetal toxicity, and retinal pigment epithelial detachment. More than 20% of patients taking pemigatinib for MLNs experience hyper- or hypophosphatemia, anemia, decreased appetite, nausea, dyspepsia, abdominal pain, diarrhea, constipation, nail toxicity, alopecia, stomatitis, dry skin, dry mouth, dry eye, blurred vision, rash, epistaxis, extremity pain, back pain, peripheral edema, and dizziness. More than 20% of patients taking it for cholangiocarcinoma experience hyper- or hypophosphatemia, decreased appetite, nausea, vomiting, diarrhea, dysgeusia, abdominal pain, constipation, nail toxicity, alopecia, stomatitis, dry skin, dry mouth, dry eye, arthralgia, and back pain.
Avoid concurrent use of CYP3A inducers and inhibitors. Reduce the pemigatinib dose if a CYP3A inhibitor is unavoidable.
Ensure patients adhere to comprehensive ophthalmologic examinations, including optical coherence tomography, prior to initiation and every two months for the first six months, every three months for the duration of treatment, and urgently as needed if they develop new visual symptoms.
Monitor patients for hyperphosphatemia. For serum phosphate levels greater than 5.5 mg/dl, educate them about following a low-phosphate diet. For phosphate levels greater than 7 mg/dl, consult the provider for phosphate-lowering therapy and, depending on severity, withholding, reducing, or permanently discontinuing pemigatinib.
Verify pregnancy status of patients of reproductive potential prior to initiating therapy.
- Report any visual symptoms, such as blurred vision, floaters, or photopsia.
- Because of the risk for embryo-fetal toxicity, use effective contraception during treatment and for one week after your last dose.
- Do not breastfeed during treatment and for one week after your last dose.
The clinical trials demonstrated no difference in safety or effectiveness in adult patients of different ages, races, or ethnicities. Safety and effectiveness have not been established in pediatric patients.
Pemigatinib is considered a hazardous drug because it can cause embryo-fetal toxicity.
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