Results of the global phase 2 FOENIX-CCA2 trial support the efficacy and safety of futibatinib treatment in patients with locally advanced or metastatic unresectable intrahepatic CCA and FGFR2 fusions or rearrangements, and indicate that futibatinib does not adversely affect patients’ quality of life.
Data were analyzed in 2 phase 2 studies of futibatinib, a highly selective irreversible fibroblast growth factor receptor (FGFR)1-4 inhibitor, from the FOENIX-CCA2 clinical trial. Results were presented at this year’s virtual meeting of the European Society for Medical Oncology (ESMO).
An ongoing, global, open-label phase 2 clinical trial, FOENIX-CCA2 enrolled patients with locally advanced or metastatic unresectable intrahepatic CCA and FGFR2 fusions or rearrangements. Approximately 10% to 20% of patients with CCA have FGFR2 fusions.
Of the 103 patients who participated in FOENIX-CCA2, 67 were included in each of the 2 studies presented at ESMO. The first study analyzed efficacy and safety data. The second study evaluated quality-of-life (QOL) outcomes. In 2018, the FDA granted futibatinib an orphan drug status.
Efficacy and Safety in FOENIX-CCA2
In the first study, data from the FOENIX-CCA2 clinical trial were presented by John A. Bridgewater, PhD, FRCP, Professor of Medical Oncology, Department of Medical Oncology, University College London Cancer Institute, England, and colleagues. A total of 67 patients received futibatinib and had a minimum of 6-month follow-up. Most of these patients (82%) had FGFR2 fusions.
The primary study end point was the objective response rate (ORR), as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 criteria; this end point was confirmed by a second tumor assessment 4 to 6 weeks after the initial response. Secondary end points included the duration of response, disease control rate, progression-free survival, and safety.
The ORR with futibatinib was 37.3%; median duration of response was 8.3 months, and 37% of the patients are still receiving treatment. The subgroup analysis showed that patients aged ≥65 years had a better ORR than did patients aged <65 years (57.1% vs 32.1%, respectively). In addition, this analysis showed that female patients had a better ORR than male patients (43.6% vs 28.6%, respectively).
Adverse events reported were consistent with those seen in other FGFR inhibitors. Of note, patients who responded to treatment with futibatinib had higher phosphate levels than did nonresponders. This is noteworthy because hyperphosphatemia was the most common adverse event in patients who received futibatinib.
A phase 3 clinical trial of futibatinib versus gemcitabine and cisplatin for the first-line treatment of patients with intrahepatic CCA and FGFR2 rearrangements is underway.
Quality-of-Life Study in FOENIX-CCA2
In the second study, the health-related quality of life (QOL) data from the FOENIX-CCA2 clinical trial were examined. This is the first report of QOL data for an FGFR inhibitor in patients with intrahepatic CCA. Patient-reported outcomes (PROs) from the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EuroQol-5D (EQ-5D-3L) QOL instruments were collected by Juan W. Valle, MB ChB, MSc, FRCP, Division of Cancer Sciences, University of Manchester, England, and colleagues.
The EORTC QLQ-C30 is composed of 5 multi-item scales (ie, physical, role, social, emotional, and cognitive functioning) and 9 single items (ie, pain, fatigue, financial impact, appetite loss, nausea/vomiting, diarrhea, constipation, sleep disturbance, and QOL). The EQ-5D-3L is a QOL measure with 1 question for each of 5 dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
A total of 67 patients were included in the interim analysis, of whom 57 (85%) had PROs available. The investigators collected patient-reported outcomes at screening, at cycles 2 and 4, every 3 cycles, and then at the end of treatment. Mean QLQ-C30 score was sustained and stable in terms of individual function and symptom measures from baseline through treatment cycle 13 (ie, 273 days) of futibatinib.
A worsening of constipation at cycles 2 and 4 (+12.4 and +10.7 points, respectively) was the only clinically meaningful increase in QLQ-C30 score (ie, an increase of ≥10 points). The mean EQ-5D-3L score showed an increasing trend from baseline to cycle 13. This suggests that patients had improved QOL and health.
Source: Bridgewater J, et al. Ann Oncol. 2020;31(4_suppl). Abstract 58P.