The First Targeted Drug for Bile Duct Cancer Receives FDA Approval

For patients with advanced, previously treated intrahepatic bile duct cancer (cholangiocarcinoma) who have an FGFR alteration, accelerated approval was granted to the drug pemigatinib (Pemazyre) on 17 April 2020 by the US Food and Drug Administration (FDA).

Important News for Oncology

With this development, we now have an FDA-approved option we can rely on for a type of cancer that has been extremely challenging to treat.

Cholangiocarcinoma is a rare type of cancer that develops in the bile ducts, the narrow tubes that carry bile, a fluid that aids digestion, from the liver to the gallbladder and small intestine.

Today's approval covers tumors that are locally advanced (the cancer has grown beyond the organ where it began but has not yet spread to distant parts of the body) or metastatic (cancer cells have spread to other parts of the body), with a fibroblast growth factor receptor 2 (FGFR2) gene fusion or other rearrangement within the tumor.

At diagnosis, most patients with cholangiocarcinoma have advanced-stage cancer, meaning that the disease can no longer be treated with surgery. Until now, there have been no FDA-approved therapies for these patients; a combination of chemotherapy drugs has been the standard initial treatment. FGFR2 fusions have been found in the tumors of approximately 9% to 14% of patients with cholangiocarcinoma. This new drug, whose active ingredient is pemigatinib, is a tablet that blocks FGFR2 to prevent tumor cells from growing and spreading.

Approval Based on the FIGHT-202 Phase-II Clinical Trial

Pemazyre's approval was based on results from 107 previously treated patients with locally advanced or metastatic cholangiocarcinoma and an FGFR2 fusion or rearrangement, enrolled in FIGHT-202, a phase-II clinical trial. During the clinical trial, patients took Pemazyre once daily for 14 consecutive days, followed by 7 days off treatment, and continued these 21-day cycles until the disease progressed or they experienced a side effect they could not tolerate. Patients were scanned every eight weeks to assess how well Pemazyre was working during the study. The trial used overall response rate as a criterion to measure how many patients experienced a complete or partial tumor response during treatment.

Results of the Study

• The overall response rate was 36%, with 3 complete responses (2.8%) and 33% partial responses.
• The disease control rate was 82%.
• Median progression-free survival and overall survival were 6.9 months and 21.1 months, respectively.
• The most common side effect was mild (grade 1-2) hyperphosphatemia (elevated blood phosphate; frequency 60%), which could primarily be managed through dietary modifications and phosphate binders. The most common side effects occurring in 20% or more of patients taking Pemazyre were hyperphosphatemia and hypophosphatemia (electrolyte disturbances), alopecia (hair loss), diarrhea, nail disorders, fatigue, dysgeusia (taste disturbances), nausea, constipation, stomatitis (pain or inflammation in the mouth), dry eyes, dry mouth, decreased appetite, vomiting, joint pain, abdominal pain, back pain, dry skin, and ocular (eye) toxicity.

With this approval, genetic analysis of the tumor has become a new standard for patients diagnosed with advanced cholangiocarcinoma

As a condition of this accelerated approval, the sponsor company will complete and submit the results of a randomized phase-III trial showing an improvement in progression-free survival or overall survival.