Is pemetinib/pemetinib targeted drug effective?

Pemigatinib is a targeted drug that targets changes in the fibroblast growth factor receptor (FGFR) 2 gene and is used to treat cholangiocarcinoma. This drug is selective and potent, inhibiting the activity of FGFR1, 2 and 3. One study evaluated the safety and antitumor activity of pemetinib in previously treated patients with locally advanced or metastatic cholangiocarcinoma who may or may not have FGFR2 fusions or rearrangements.

The study (FIGHT-202) is a multi-center, open-label, single-arm, multi-phase clinical trial. Patients were included in the study if they were 18 years of age or older, had disease progression on at least one prior treatment, and had an ECOG score of 0-2. The study divided patients into three cohorts: patients with FGFR2 fusions or rearrangements, patients with other FGF/FGFR mutations, or patients without FGF/FGFR mutations. All enrolled patients took pemetinib daily, with an initial dose of 13±5 mg once daily (21-day cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, withdrawal of consent, or physician decision. The primary endpoint was to assess the proportion of patients with FGFR2 fusions or rearrangements who achieved an objective response and was assessed centrally in all patients who received at least one dose of pemetinib.

A total of 146 patients participated during the study period, of which 107 patients had FGFR2 fusions or rearrangements, 20 patients had other FGF/FGFR mutations, 18 patients had no FGF/FGFR mutations, and 1 patient had an undetermined FGF/FGFR mutation. These patients were followed for a median of 17.8 months (IQR, 11.6-21.3 months). The results showed that 38 patients (35.5% [95% CI, 26.5-45.4]) with FGFR2 fusion or rearrangement achieved objective response, including 3 complete responses and 35 partial responses.

Overall, hyperphosphatemia was the most common adverse event regardless of cause, although the incidence was modest. Grade 3 or worse adverse events (regardless of cause) occurred in 64% of patients, with the most common including hypophosphatemia, arthralgia, stomatitis, hyponatremia, and abdominal pain. Serious adverse events occurred in 45% of patients, the most common of which were abdominal pain, pyrexia, cholangitis, and pleural effusion. During the study period, 49% of patients died, with the most common cause of death being disease progression. No treatment-related deaths were noted.

These data indicate that prior exposurePemetinib has therapeutic potential in patients with cholangiocarcinoma with FGFR2 fusions or rearrangements. However, further research is needed to confirm its long-term safety and effectiveness and provide a more adequate basis for clinical practice.