Yvonne Riley-Poku, PharmD

 (Truseltiq; QED Therapeutics) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor 2 (FGFR2) fusion or other rearrangement.

 Continued approval of this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

The FDA granted the application priority review, fast-track designation, and orphan drug designation.

Cholangiocarcinoma is a rare bile duct cancer, with physicians diagnosing approximately 8000 cases each year.

 Physicians select patients for infigratinib treatment based on the presence of FGFR2 fusion or rearrangement detected using an FDA-approved companion diagnostic test, FoundationOne CDx.

The FDA approval was based on a multicenter, open-label, single-arm phase 2 trial. Study investigators enrolled 108 patients who had undergone a previous treatment for unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement as determined by local or central testing.

Patients received infigratinib 125 mg daily for 21 consecutive days, in 28-day cycles until disease progression or unacceptable toxicity.

The trial’s efficacy measures were overall response rate (ORR) and duration of response (DoR). The ORR was 23% (1 complete response and 24 partial responses), and the average DoR was 5 months. The median time to response was 3.6 months.

Infigratinib inhibits fibroblast growth factor receptor (FGFR) signaling and decreases cell proliferation in cancer cell lines with activating FGFR amplifications, mutations, or fusions.

The recommended infigratinib dose is 125 mg (one 100 mg capsule and one 25 mg capsule) orally once a day for 21 consecutive days followed by 7 days off therapy in 28-day cycles. Patients continue treatment until disease progression or unacceptable toxicity.

Before beginning therapy with infigratinib, female patients must tell their health care provider whether they are pregnant or plan to become pregnant. Infigratinib can cause fetal harm when taken by pregnant women.

 Serious adverse events (AEs) include ocular toxicity and hyperphosphatemia.

Common AEs include hyperphosphatemia, increased creatinine, nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, blurred vision, and vomiting.

Certain medications have effects on infigratinib. Patients must avoid concomitant use of infigratinib with these medications:

Strong and moderate CYP3A inhibitors may increase infigratinib plasma concentrations, thus increasing the risk of AEs.

Strong and moderate CYP3A inducers may decrease infigratinib plasma concentrations, thus reducing infigratinib anti-tumor activity.

Gastric acid reducing agents (e.g., proton pump inhibitors, H2-antagonists, and locally acting antacids) may decrease infigratinib plasma concentrations thus reducing infigratinib anti-tumor activity. If coadministration cannot be avoided, providers must advise patients to stagger infigratinib administration from H2-antagonists and locally acting antacids at appropriate time intervals.

Pharmacists need to counsel patients on several points:

Infigratinib can cause fetal harm when taken by pregnant women. Females of reproductive potential must use effective contraception during treatment and for 1 month after the final dose. Males with female partners of reproductive potential must also use effective contraception during treatment with infigratinib and for 1 month after final dose.

Patients must not breastfeed during treatment and for 1 month after the final infigratinib dose.

Infigratinib can cause retinal pigment epithelial detachment, causing symptoms such as blurred vision. Providers must perform ophthalmic examinations including optical coherence tomography (OCT) before initiating infigratinib therapy, and then at 1 month, 3 months, and every 3 months thereafter for the duration of treatment. When ocular toxicity occurs, providers must continue ophthalmic evaluations, modify dose, or withhold medication appropriately.

Infigratinib can elevate phosphate levels, leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis, vascular calcification, and myocardial calcification. Providers must monitor blood phosphate levels throughout treatment and withhold, reduce dose, or permanently discontinue infigratinib depending on duration and severity of hyperphosphatemia.

Patients must take infigratinib on an empty stomach at least 1 hour before or 2 hours after food. Patients must swallow capsules whole with a glass of water at approximately the same time each day. When patients miss a dose by 4 or more hours or if vomiting occurs, they must resume the regular daily dose schedule the next day.

Clinical Oncology News. FDA Watch. FDA approves Truseltiq for some advanced cholangiocarcinoma patients. June 4, 2021. Accessed July 19, 2021.

Truseltiq. Prescribing information. QED Therapeutics;2021. Accessed July 19, 2021. 

https://www.truseltiq.com/pdfs/prescribing-information.pdf

U.S Food and Drug Administration. FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma. May 28, 2021. Accessed July 18, 2021. 

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-infigratinib-metastatic-cholangiocarcinoma

American Cancer Society. Bile duct cancer. Accessed July 19, 2021. 

https://www.cancer.org/cancer/bile-duct-cancer.html

Articles

Oncology Overview: Infigratinib for Advanced Cholangiocarcinoma

Multiple myeloma (MM) is a cancer that forms in plasma cells. Healthy plasma cells are an important part of the immune system and help fight infections. In MM, cancerous plasma cells producing abnormal proteins overwhelm healthy blood cells and cause complications including fatigue, anemia, and the inability to fight infections.

MM is rare, with fewer than 200,000 cases occurring annually in the United States.

 The American Cancer Society estimates that oncologists will diagnose about 34,920 new cases of MM in 2021 with about 12,410 deaths expected to occur.

Therapy for MM may include a combination of targeted therapy, immunotherapy, corticosteroids, chemotherapy, radiation therapy, and bone marrow transplants.

The thalidomide analogues lenalidomide (Revlimid; Bristol Myers Squibb) and pomalidomide (Pomalyst; Celegene) are immunomodulating drugs for the treatment of MM.

 Thalidomide, a known human teratogen, causes serious birth defects or embryo-fetal death. Since lenalidomide and pomalidomide are related to thalidomide, they have similar teratogenic adverse effects.

The FDA initially approved lenalidomide in 2005 for treatment of transfusion dependent myelodysplastic syndrome. In 2015, the FDA approved pomalidomide when its indication was expanded to include treatment of MM in combination with dexamethasone. Further, the FDA approved the first generic product lenalidomide in 2021.

Pomalidomide was initially approved by the FDA as an orphan drug in 2013 for patients with multiple myeloma. Pomalidomide is also available as a generic product with the FDA approving the first generic pomalidomide product in 2020.6 (see 

Patients must read and agree to all the instructions in the appropriate REMS programs before initiating therapy. Lenalidomide and pomalidomide may cause serious adverse effects including the following:

—Patients must not use lenalidomide or pomalidomide during pregnancy. These medications may cause birth defects or embryo-fetal death. Females of reproductive potential must prevent pregnancy before, during, and after treatment by using 2 reliable contraception methods. Male and female patients must comply with all contraceptive requirements in the REMS programs.

—Lenalidomide and pomalidomide can cause deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Thromboprophylaxis is recommended. Providers should base the choice of regimen on an assessment of the patient’s underlying risk factors.

—Lenalidomide can cause significant neutropenia and thrombocytopenia. Providers must monitor patients with neutropenia for signs of infection. Patients must watch for bleeding and bruising especially when they use other medication that may increase bleeding risk.

 is a non-credit lecturer for the Pharmacy Technician Certification Program at Housatonic Community College, Bridgeport, Connecticut.

Multiple Myeloma. Mayo Clinic. Updated June 16, 2021. Accessed July 14, 2021. 

https://www.mayoclinic.org/diseases-conditions/multiple-myeloma/symptoms-causes/syc-20353378

About Multiple Myeloma. American Cancer Society. Accessed July 14, 2021. 

https://www.cancer.org/cancer/multiple-myeloma/about.html

Revlimid. Prescribing information. Bristol Myers Squibb;2019. Accessed July 14, 2021. 

https://packageinserts.bms.com/pi/pi_revlimid.pdf

Pomalyst. Prescribing information. Bristol Myers Squibb;2020. Accessed July 14, 2021. 

https://packageinserts.bms.com/pi/pi_pomalyst.pdf

Revlimid FDA approval history. Drugs.com. Updated September 7, 2020. Accessed July 14, 2021. 

https://www.drugs.com/history/revlimid.html

Pomalyst FDA approval history. Drugs.com. Updated March 16, 2021. Accessed July 14, 2021. 

https://www.drugs.com/history/pomalyst.html

The American Cancer Society estimates that oncologists will diagnose about 34,920 new cases of multiple myeloma in 2021 with about 12,410 deaths expected to occur.