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

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 (ClinicalTrials.gov 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.