Basilea’s promising asset showed meaningful clinical benefit in patients with FGFR2 fusions intrahepatic cholangiocarcinoma

CCA represents one of the biggest challenges that the scientific community, at multiple levels, beyond hepatologists, and oncologists, is currently coping with. Also, because of its major aggressiveness and a late stage diagnosis at an advanced stage, the improvement in the clinical management of CCA has been extremely limited. Intrahepatic cholangiocarcinoma is the second most common primary liver malignancy and it has been rising in incidence over the past several decades. FGFR2 gene rearrangements in iCCA patients occur in approximately 10-16%, and this underscores the importance of next-generation sequencing in this population. Given its poor prognosis and diagnosis at a late stage, novel therapies are urgently needed to improve the outcomes. Although, there are currently several US FDA approved medications that can help target this change in the tumor, but these drugs have found to be lose effectiveness after several months as the tumor becomes resistant to the medication. Currently surgical resection is the only option to cure the disease despite its high recurrence rates. Other than surgery, only pemigatinib and infigratinib are approved for FGFR2 mutated iCCA.

The safety and ITT population comprises 147 patients: 103 with FGFR2 fusions and 44 with FGFR2 mutations or amplifications. Patients with FGFR2 fusions received a median number of 28-days treatment cycles of 7.0 compared to 5.0 treatment cycles in patients with a dose intensity of 95% in both cohorts. The objective response rate and disease control rate was 22.3%/75.7% in patients with FGFR2 fusions and 6.8% / 63.6% in patients with FGFR2 mutations or amplifications. Median PFS and OS (months) were 7.8 / 17.2 in patients with FGFR2 fusions and 8.3 / 15.9 in patients with FGFR2 mutations or amplifications. The median duration of response 6.4 months in patients with FGFR2 fusions and 5.6 for patients with FGFR2 mut/amp. Also, patients who observed progressive disease was observed in 15.5% in patients with FGFR2 fusions and 20.5% in patients with FGFR2 mut/amp.

Severe (Grade 3) drug-related AEs were infrequent with the exception of AST and ALT elevations; no cases of drug-induced liver injury (DILI) were assessed. 

Conclusion- These new effective results may surely give an advantage to derizantinib in the second-line treatment setting and fulfill the unmet need of the patients with FGFR2 mutated iCCA. As we already know that currently, there are only two FDA approved therapies for FGFR mutated CCA but, as already mentioned these approved therapies lack effectiveness after several months as tumor becomes resistant to medications. So, patients with this mutation need a treatment modality, which is effective enough and capable of completely removing the tumor from the body and derazantinib can prove to be beneficial for this patient segment and fulfilling the unmet need that exists.

Expert Opinion: “This outcome is very encouraging and further strengthens the evidence for the differentiation of derazantinib versus other FGFR inhibitors both from the efficacy and safety perspective.”

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