What is pemigatinib?
Pemigatinib is a fibroblast growth factor receptor (FGFR) kinase inhibitor. Pemigatinib is an oral agent that binds to and inhibits FGFR1, FGFR2, and FGFR3 enzymes. FGFR inhibition disrupts the phosphorylation step and decreases FGFR-related signaling and decreases cells within the cell lines expression FGFR genetic alterations. FGFR inhibition leads to decreased proliferation in FGFR 1/2/3 overexpressing tumor cells.
Pemigatinib was granted accelerated approval by the FDA for the treatment of previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement as detected by FoundationOne(R) CDX, an FDA-approved companion diagnostic test.
Pemigatinib was approved based on the result of the FIGHT-202 trial, an open-label, phase II, single-arm trial in 107 patients with locally advanced unresectable or metastatic cholangiocarcinoma who had disease progression while on treatment or after at least one prior line of therapy and had an FGFR2 gene fusion or rearrangement. Pemigatinib was dosed as 13.5 mg orally once daily for 14 days followed by 7 days off therapy of a 21-day cycle. The primary efficacy endpoint was overall response rate (ORR) as well as duration of response (DOR).
The ORR was 36 percent (95% CI 27-45), with 3 complete responses and 35 partial responses. The median DOR was 9.1 months (95% CI 6-14.5) with 63 percent (24/38 patients) of patients observing a response greater than 6 months and 18 percent (7/38 patients) of patients having a response greater than 12 months (Lancet Oncol 2020; S1470-2045).
How do you administer this drug?
Pemigatinib is given as 13.5 mg orally daily for 14 days followed by 7 days off on a 21-day cycle. No premedications are needed.
What are the common side effects associated with pemigatinib (> or =10%)?
* General: fatigue (42%), headache (16%), anorexia (16%)
* Cardiovascular: peripheral edema (18%)
* Dermatologic: alopecia (49%), nail changes (43%), palmar-plantar erythrodysesthesia (15%), xeroderma (20%)
* Endocrine: hyperphosphatemia (60-92%), hypophosphatemia (23%), hypoalbuminemia (34%), hypocalcemia (17%), hypoglycemia (11%), hypokalemia (26%), hyponatremia (39%), dehydration (15%), hypercalcemia (43%), hyperglycemia (36%), hyperuricemia (30%)
* GI: diarrhea (47%), nausea (40%), stomatitis (35%), vomiting (27%), xerostomia (34%)
* Hematologic: anemia (43%), leukopenia (18%), lymphocytopenia (36%), thrombocytopenia (28%)
* Hepatic: elevated ALT (43%), elevated AST (43%), elevated Alk Phos (41%), hyperbilirubinemia (26%)
* Renal: elevated creatinine (41%)
* Ophthalmic: dry eye syndrome (27-35%)
What are uncommon side effects?
Additional side effects include cholangitis (>/= 2%), intestinal obstruction (>/= 2%), retinal pigment epithelium detachment (6%), acute renal failure (>/= 2%), and pleural effusions (>/= 2%).
Are there any important drug interactions?
Pemigatinib is metabolized by CYP3A. As such, coadministration with strong and moderate CYP3A inducers may decrease concentrations of pemigatinib and should be avoided. Dose reductions are required when coadministered with strong and moderate CYP3A inhibitors.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
There are no known renal dose adjustments, but pemigatinib has not been studied in patients with GFR < 30 mL/min using MDRD. There are no dose adjustments for mild or moderate hepatic impairment, but severe hepatic impairment has not been evaluated.
Practical tips
* Hyperphosphatemia occurred in 92 percent of patients with the median time to onset of 8 days (1-169 days). Phosphate-lowering agents were required for 29 percent of patients.
* Retinal pigment epithelial detachment was observed with a median time to onset of 62 days. Dry eye occurred in 27 percent of patients. Recommendations for artificial tear eye drops should be considered to reduce the incidence of dry eye.
What should my patients know about pemigatinib?
Patients should contact their health care provider if they experience any of the following:
* Vision changes (blurred vision, flashes of light, or see black spots)
* Muscle cramps or numbness or tingling around the mouth
What else should I know about pemigatinib?
* Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is > 5.5 mg/dL.
* If the serum phosphate level is > 7 mg/dL but
* If the serum phosphate level is > 10 mg/dL, follow similar recommendations; however, therapy should be withheld if levels are not >/= 10 mg/dL within 1 week. Resume pemigatinib at a dose reduction once phosphate level is < 7 mg/dL.
* Perform a comprehensive ophthalmological exam prior to initiation of therapy and every 2 months for the first 6 months and every 3 months thereafter during treatment.
What useful links are available?
* Accelerated approval for cholangiocarcinoma with an FGFR2 rearrangement or fusion: https://bit.ly/35tIMlZ
* Approval for patients with cholangiocarcinoma, a cancer of bile ducts: https://bit.ly/3d6hCnJ
Any clinical trials for pemigatinib?
Clinical trials with pemigatinib are ongoing evaluating the response compared to standard-of-care chemotherapy for cholangiocarcinoma, as well as evaluation in the treatment of urothelial carcinoma, advanced malignancies with FGFR alterations. More information is available about the clinical trials at https://clinicaltrials.gov.
JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/ Manager, Clinical Pharmacy Services at Washington University School of Medicine Saint Louis, Mo. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.