The Lynx Group
Cholangiocarcinoma News

Integrated Safety Analysis of Futibatinib in Advanced Solid Tumors, Including Intrahepatic CCA

2021 Year in Review: Cholangiocarcinoma — December 17, 2021

Results of this retrospective pooled safety analysis indicate that futibatinib was safe and tolerable in patients with advanced solid tumors, including intrahepatic CCA.

An integrated safety analysis evaluated the safety profile of the recommended phase 2 dose (RP2D) of the irreversible FGFR1-4 inhibitor futibatinib (20 mg once daily) across tumor types. Results of the safety analysis were reported at the 2021 European Society for Medical Oncology Annual Congress.

The retrospective safety analysis included patients who received ≥1 futibatinib doses at 20 mg once daily in a global phase 1/2 trial ( Identifier: NCT02052778) and a Japanese phase 1 study (JapicCTI-142552). The safety analysis included adverse events (AEs), treatment-related adverse events (TRAEs), AEs of special interest (AESIs), and time to onset/resolution of AESIs. The data cutoff date was October 1, 2020.

At data cutoff, a total of 318 patients had received futibatinib 20 mg once daily across the 2 trials for a median duration of 111 days. The median age of the analysis population was 59 years. The most common tumor type was cholangiocarcinoma (CCA; 60% of patients); 98% of the participants had received ≥1 prior treatments.

Overall, TRAEs of any grade were experienced by 99% of futibatinib-treated patients, 43% of patients experienced grade 3 TRAEs and 1% experienced grade 4 TRAEs. No treatment-related deaths were reported. The most common grade ≥3 TRAEs were hyperphosphatemia (23%), increased alanine aminotransferase (6%), and increased aspartate aminotransferase (5%). Grade ≥3 events that occurred in <3% of patients included diarrhea, nausea, stomatitis, and fatigue. In most instances, grade 3 hyperphosphatemia resolved with phosphate binders and dose adjustments, with a median time of resolution of 7 days. Other AESIs included nail toxicities, hepatotoxicity, and palmar-plantar erythrodysesthesia, which were mostly mild to moderate in severity. Hepatotoxicity occurred in 30% of patients, which involved primarily liver enzyme elevations. Retinal toxicities occurred in 8% of patients, which were all of grade 1/2 severity. Treatment-related cataracts developed in 2% of patients, and retinal pigment epithelial detachment occurred in 1%. Median time to resolution of most grade 3 TRAEs ranged from 7 to 8 days. TRAEs were managed mostly with dose adjustments (54%). Treatment discontinuations due to AEs were reported in 3% of patients.

Results of this integrated safety analysis indicate that futibatinib is safe and tolerable in patients with advanced solid tumors, including intrahepatic CCA, with the majority of TRAEs of mild severity and most grade ≥3 events resolving with adequate management.

Source: Meric-Bernstam F, Furuse J, Oh D, et al. Pooled analysis safety profile of futibatinib in patients with advanced solid tumors, including intrahepatic cholangiocarcinoma (iCCA). Ann Oncol. 2021;32(suppl_5):S376-S381.

Related Items

Phase 1 Results of Gunagratinib in Patients with Advanced Solid Tumors Harboring FGFR Pathway Alterations
2021 Year in Review: Cholangiocarcinoma
A phase 1/2a, first-in-human clinical study demonstrated that the highly selective, irreversible pan-FGFR inhibitor gunagratinib was safe and well-tolerated in patients with advanced solid tumors, including CCA.
Prognostic Value of FGFR2 Alterations in Patients Receiving Systemic Chemotherapy for Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
A retrospective analysis indicated the prognostic value of FGFR2 fusions/rearrangements in patients with intrahepatic CCA receiving systemic chemotherapy, which warrants additional study.
FGFR2 Fusion and/or Rearrangement Profiling in Chinese Patients with Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
Epidemiologic data assessed the incidence rate of FGFR2 gene fusion or rearrangement in Chinese patients with intrahepatic CCA, including those with heterogeneous FGFR2 partner genes.
A Comprehensive Genomic and Immune Profiling Study of IDH1- and IDH2-Driven Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
A comprehensive genomic and immune characterization of IDH-mutated and wild-type intrahepatic CCA revealed significant differences in genetic alterations.
Characteristics of IDH Mutations in Bile Duct Carcinoma in a Chinese Population
2021 Year in Review: Cholangiocarcinoma
A retrospective analysis in a large Chinese patient cohort with bile duct carcinoma indicated that activating IDH1/2 mutations occurred at a lower rate compared with that previously reported in the global population.
Silmitasertib (CX-4945) plus Gemcitabine and Cisplatin as First-Line Treatment for Patients with Locally Advanced or Metastatic CCA
2021 Year in Review: Cholangiocarcinoma
Preliminary evidence suggests that combination treatment with silmitasertib plus gemcitabine/cisplatin as first-line therapy has promising efficacy and a favorable safety profile in patients with locally advanced or metastatic CCA.
Targeted Therapies in CCA: Assessment of US Oncologist Practice Patterns
2021 Year in Review: Cholangiocarcinoma
Findings from a clinical practice assessment identified gaps in knowledge, competence, and confidence regarding testing and the use of targeted therapies in patients with unresectable CCA, underscoring the important role of education in overcoming these gaps.
First-Line Toripalimab plus Lenvatinib in Combination with GemOx Chemotherapy for Advanced Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
Results of a phase 2 study indicate that toripalimab and lenvatinib in combination with GemOx chemotherapy provide antitumor activity and reasonable tolerability in patients with advanced intrahepatic CCA.
Comparative Landscape of Actionable Somatic Alterations in Advanced CCA from Circulating Tumor and Tissue-Based DNA Profiling
2021 Year in Review: Cholangiocarcinoma
Findings from a retrospective analysis support the use of both tissue and liquid biopsy biomarker testing to guide therapy selection in patients with advanced CCA, particularly when tissue may not be readily available.
Tibsovo (Ivosidenib) FDA Approved for Advanced or Metastatic Cholangiocarcinoma and IDH1 Mutation
By Loretta Fala
2021 Year in Review: Cholangiocarcinoma
Cholangiocarcinoma (CCA) is an aggressive cancer of the bile duct that forms inside the liver (ie, intrahepatic) or outside the liver (ie, extrahepatic, including perihilar and distal tumors). Individuals with colitis or certain liver diseases may have an increased risk for CCA. Although the precise incidence of CCA is unknown, an estimated 8000 new cases of CCA are diagnosed annually in the United States. It is likely, however, that this number is higher, because CCA is difficult to diagnose and may be misclassified at times.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: