福巴替尼治疗胆管癌的效果？

Forbatinib (LYTGOBI) was developed by Taiho Oncology, a subsidiary of Japan's Taiho Pharmaceutical. It was approved by the US FDA for marketing on September 30, 2022, with the trade name Lytgobi. It is used to treat adult patients with locally advanced or metastatic intrahepatic cholangiocarcinoma with fibroblast growth factor receptor 2 (FGFR2) gene fusion. It is an irreversibly covalently bound FGFR inhibitor. Other approved FGFR inhibitors are all reversible ATP competitive inhibitors. So, how effective is forbatinib in treating cholangiocarcinoma?

The effect of forbatinib in the treatment of cholangiocarcinoma

TAS-120-101 (NCT02052778) is a multicenter, open-label, single-arm trial evaluating LYTGOBI in 103 patients with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma. Using next-generation sequencing (NGS) testing, the presence of FGFR2 fusions or other rearrangements was determined in 102 enrolled patients (99%). Eligible in-frame fusions and other rearrangements are predicted to have a breakpoint in intron 17/exon 18 of the FGFR2 gene, leaving the FGFR2 kinase domain intact.

Patients received LYTGOBI, 20 mg orally once daily, until disease progression or unacceptable toxicity. The primary efficacy outcome measures were overall response rate (ORR) and duration of response (DoR) as determined by an independent review committee (IRC) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Trial population characteristics were: median age 58 years (range: 22-79 years), 22% of patients ≥65 years, 56% female, race/ethnicity: 50% white, 29% Asian, 8% black or African American, 1% Native Hawaiian or other Pacific Islander, 13% unknown race, baseline Eastern Cooperative Oncology Group (ECOG) performance status 0 (47%) or 1 (53%). Seventy-eight percent of patients (78%) had in-frame FGFR2 gene fusions, with the most common FGFR2 fusion partner being BIC 1 (n = 24, 23%). Twenty-two percent of patients (22%) had additional FGFR2 rearrangements that were not in the same frame as the partner gene or that could not identify the partner gene.

All patients had received at least 1 systemic treatment, 30% had 2 treatment options, and 23% had 3 or more treatment options. All patients had received platinum therapy, and 91% had received gemcitabine/cisplatin therapy.

Table 1 summarizes the efficacy results. The median time to response was 2.5 months (range, 0.7–7.4 months).

Table 1: TAS efficacy results-120-101

Recommended related articles: